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First-in-class ADC has benefit across mTNBC subgroups
But both an observer and the lead study author cautioned that the results were hypothesis generating.
Nonetheless, the data suggest the drug yields good survival outcomes in comparison with placebo in both BRCA1/2-positive and -negative patients and is effective even for those with low expression of the target protein, trophoblast cell surface antigen 2 (Trop-2).
The research was presented at the San Antonio Breast Cancer Symposium (SABCS) 2020.
Study presenter Sara Hurvitz, MD, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, urged caution in interpreting the data, given the small sample sizes in the Trop-2–low subgroup and germline BRCA1/2-positive subgroup.
Jennifer K. Litton, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, who was not involved in the research, echoed those comments.
She told Medscape Medical News that the numbers, particularly for the BRCA1/2 analysis, were “very small.”
She added: “This was not a prespecified group, so it represents an interesting analysis to be hypothesis generating for future studies but not anything applicable to current clinical practice.”
Nevertheless, Litton said the data from the primary analysis of ASCENT remain “practice changing” for women with mTNBC who have received at least two previous lines of therapy.
As to whether SG will eventually move beyond this advanced setting, she emphasized that “more trials would need to be done and reported evaluating its role in other settings, and hopefully expanding its usefulness for patients.”
SG is a first-in-class drug comprising an antibody directed at Trop-2, which is highly expressed in breast cancer, and linked to SN-38, the active metabolite of irinotecan.
On the basis of positive phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with mTNBC who experience disease progression after at least two prior therapies.
As reported by Medscape Medical News, primary results from ASCENT that were presented at ESMO 2020 showed that SG improved progression-free survival (PFS) by nearly 4 months and overall survival by more than 5 months for women with pretreated mTNBC compared to chemotherapy.
Study details
At SABCS, Hurvitz presented an exploratory biomarker evaluation of data from the trial regarding the association between SG efficacy and Trop-2 expression, as well as germline BRCA1/2 mutation status.
She reminded the audience that, in ASCENT, 529 patients with mTNBC who had experienced disease progression after undergoing at least two chemotherapy regimens for advanced disease were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or physician’s choice of treatment.
Treatment was continued until disease progression or unacceptable toxicity occurred.
For the current analysis, which focused on patients who did not have brain metastases, the team studied primary or metastatic archival biopsy or surgical specimens collected at study entry.
These were analyzed using a validated immunohistochemistry assay. Tumors were categorized as Trop-2–low, –medium, or –-high expressers on the basis of H-score, which is a weighted summation of percent staining. In addition, germline BRCA1/2 mutation status was determined at baseline.
Mutation status was known for 149 SG patients and 143 control patients. Of those, the majority (57% and 54%, respectively) were BRCA1/2 negative.
Among 151 SG patients for whom Trop-2 expression status was available, 56% had tumors of high expression; 26%, medium expression; and 18%, low expression. In the control group, Trop-2 expression was known in 139 patients, of whom 52% had tumors of high expression; 25%, medium expression; and 23%, low expression.
Hurvitz reported that, although median PFS among patients given SG decreased with decreasing Trop-2 expression, it remained longer than that seen with control treatment. In patients with tumors of Trop-2–high status, median PFS was 6.9 months with SG, vs. 2.5 for patients who underwent control treatment. This fell to 5.6 months vs. 2.2 months in the Trop-2–medium group and 2.7 months vs 1.6 months in Trop-2–low group.
A similar pattern was seen for overall survival. In the Trop-2–high group, median overall survival was 14.2 months with SG, vs. 6.9 months with control therapy; 14.9 months vs. 6.9 months in the Trop-2–medium group; and 9.3 months vs. 7.6 months in the Trop-2–low group.
Again, the objective response rate fell from 44% to 38% and then to 22% with SG in the Trop-2–high, –medium, and –low groups, compared with 1%, 11%, and 6%, respectively, with control treatment.
There did not seem to be any interaction between Trop-2 expression and treatment-related adverse events of special interest. Rates of neutropenia, diarrhea, and anemia were consistently higher in SG-treated patients than in those given placebo.
Hurvitz said the objective response rate was markedly higher with SG vs. control treatment in both BRCA1/2-positive and -negative patients, at 19% vs. 6% in the positive group and 33% vs. 6% in the negative group.
This was reflected in improved median PFS with SG in both subgroups, at 4.6 months vs. 2.5 months with control therapy in BRCA1/2-positive patients and 4.9 months vs. 1.6 months in BRCA1/2-negative patients.
Overall survival was 15.6 months with SG, vs. 4.4 months with control treatment in BRCA1/2-positive patients. In BRCA1/2-negative patients, the respective figures were 10.9 months and 7.0 months.
The study was sponsored by Immunomedics. Hurvitz has financial ties to Immunomedics and multiple other pharmaceutical companies. Litton has financial ties to multiple companies, including Medscape and companies developing and marketing breast cancer therapies.
This article first appeared on Medscape.com.
But both an observer and the lead study author cautioned that the results were hypothesis generating.
Nonetheless, the data suggest the drug yields good survival outcomes in comparison with placebo in both BRCA1/2-positive and -negative patients and is effective even for those with low expression of the target protein, trophoblast cell surface antigen 2 (Trop-2).
The research was presented at the San Antonio Breast Cancer Symposium (SABCS) 2020.
Study presenter Sara Hurvitz, MD, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, urged caution in interpreting the data, given the small sample sizes in the Trop-2–low subgroup and germline BRCA1/2-positive subgroup.
Jennifer K. Litton, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, who was not involved in the research, echoed those comments.
She told Medscape Medical News that the numbers, particularly for the BRCA1/2 analysis, were “very small.”
She added: “This was not a prespecified group, so it represents an interesting analysis to be hypothesis generating for future studies but not anything applicable to current clinical practice.”
Nevertheless, Litton said the data from the primary analysis of ASCENT remain “practice changing” for women with mTNBC who have received at least two previous lines of therapy.
As to whether SG will eventually move beyond this advanced setting, she emphasized that “more trials would need to be done and reported evaluating its role in other settings, and hopefully expanding its usefulness for patients.”
SG is a first-in-class drug comprising an antibody directed at Trop-2, which is highly expressed in breast cancer, and linked to SN-38, the active metabolite of irinotecan.
On the basis of positive phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with mTNBC who experience disease progression after at least two prior therapies.
As reported by Medscape Medical News, primary results from ASCENT that were presented at ESMO 2020 showed that SG improved progression-free survival (PFS) by nearly 4 months and overall survival by more than 5 months for women with pretreated mTNBC compared to chemotherapy.
Study details
At SABCS, Hurvitz presented an exploratory biomarker evaluation of data from the trial regarding the association between SG efficacy and Trop-2 expression, as well as germline BRCA1/2 mutation status.
She reminded the audience that, in ASCENT, 529 patients with mTNBC who had experienced disease progression after undergoing at least two chemotherapy regimens for advanced disease were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or physician’s choice of treatment.
Treatment was continued until disease progression or unacceptable toxicity occurred.
For the current analysis, which focused on patients who did not have brain metastases, the team studied primary or metastatic archival biopsy or surgical specimens collected at study entry.
These were analyzed using a validated immunohistochemistry assay. Tumors were categorized as Trop-2–low, –medium, or –-high expressers on the basis of H-score, which is a weighted summation of percent staining. In addition, germline BRCA1/2 mutation status was determined at baseline.
Mutation status was known for 149 SG patients and 143 control patients. Of those, the majority (57% and 54%, respectively) were BRCA1/2 negative.
Among 151 SG patients for whom Trop-2 expression status was available, 56% had tumors of high expression; 26%, medium expression; and 18%, low expression. In the control group, Trop-2 expression was known in 139 patients, of whom 52% had tumors of high expression; 25%, medium expression; and 23%, low expression.
Hurvitz reported that, although median PFS among patients given SG decreased with decreasing Trop-2 expression, it remained longer than that seen with control treatment. In patients with tumors of Trop-2–high status, median PFS was 6.9 months with SG, vs. 2.5 for patients who underwent control treatment. This fell to 5.6 months vs. 2.2 months in the Trop-2–medium group and 2.7 months vs 1.6 months in Trop-2–low group.
A similar pattern was seen for overall survival. In the Trop-2–high group, median overall survival was 14.2 months with SG, vs. 6.9 months with control therapy; 14.9 months vs. 6.9 months in the Trop-2–medium group; and 9.3 months vs. 7.6 months in the Trop-2–low group.
Again, the objective response rate fell from 44% to 38% and then to 22% with SG in the Trop-2–high, –medium, and –low groups, compared with 1%, 11%, and 6%, respectively, with control treatment.
There did not seem to be any interaction between Trop-2 expression and treatment-related adverse events of special interest. Rates of neutropenia, diarrhea, and anemia were consistently higher in SG-treated patients than in those given placebo.
Hurvitz said the objective response rate was markedly higher with SG vs. control treatment in both BRCA1/2-positive and -negative patients, at 19% vs. 6% in the positive group and 33% vs. 6% in the negative group.
This was reflected in improved median PFS with SG in both subgroups, at 4.6 months vs. 2.5 months with control therapy in BRCA1/2-positive patients and 4.9 months vs. 1.6 months in BRCA1/2-negative patients.
Overall survival was 15.6 months with SG, vs. 4.4 months with control treatment in BRCA1/2-positive patients. In BRCA1/2-negative patients, the respective figures were 10.9 months and 7.0 months.
The study was sponsored by Immunomedics. Hurvitz has financial ties to Immunomedics and multiple other pharmaceutical companies. Litton has financial ties to multiple companies, including Medscape and companies developing and marketing breast cancer therapies.
This article first appeared on Medscape.com.
But both an observer and the lead study author cautioned that the results were hypothesis generating.
Nonetheless, the data suggest the drug yields good survival outcomes in comparison with placebo in both BRCA1/2-positive and -negative patients and is effective even for those with low expression of the target protein, trophoblast cell surface antigen 2 (Trop-2).
The research was presented at the San Antonio Breast Cancer Symposium (SABCS) 2020.
Study presenter Sara Hurvitz, MD, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, urged caution in interpreting the data, given the small sample sizes in the Trop-2–low subgroup and germline BRCA1/2-positive subgroup.
Jennifer K. Litton, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, who was not involved in the research, echoed those comments.
She told Medscape Medical News that the numbers, particularly for the BRCA1/2 analysis, were “very small.”
She added: “This was not a prespecified group, so it represents an interesting analysis to be hypothesis generating for future studies but not anything applicable to current clinical practice.”
Nevertheless, Litton said the data from the primary analysis of ASCENT remain “practice changing” for women with mTNBC who have received at least two previous lines of therapy.
As to whether SG will eventually move beyond this advanced setting, she emphasized that “more trials would need to be done and reported evaluating its role in other settings, and hopefully expanding its usefulness for patients.”
SG is a first-in-class drug comprising an antibody directed at Trop-2, which is highly expressed in breast cancer, and linked to SN-38, the active metabolite of irinotecan.
On the basis of positive phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with mTNBC who experience disease progression after at least two prior therapies.
As reported by Medscape Medical News, primary results from ASCENT that were presented at ESMO 2020 showed that SG improved progression-free survival (PFS) by nearly 4 months and overall survival by more than 5 months for women with pretreated mTNBC compared to chemotherapy.
Study details
At SABCS, Hurvitz presented an exploratory biomarker evaluation of data from the trial regarding the association between SG efficacy and Trop-2 expression, as well as germline BRCA1/2 mutation status.
She reminded the audience that, in ASCENT, 529 patients with mTNBC who had experienced disease progression after undergoing at least two chemotherapy regimens for advanced disease were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or physician’s choice of treatment.
Treatment was continued until disease progression or unacceptable toxicity occurred.
For the current analysis, which focused on patients who did not have brain metastases, the team studied primary or metastatic archival biopsy or surgical specimens collected at study entry.
These were analyzed using a validated immunohistochemistry assay. Tumors were categorized as Trop-2–low, –medium, or –-high expressers on the basis of H-score, which is a weighted summation of percent staining. In addition, germline BRCA1/2 mutation status was determined at baseline.
Mutation status was known for 149 SG patients and 143 control patients. Of those, the majority (57% and 54%, respectively) were BRCA1/2 negative.
Among 151 SG patients for whom Trop-2 expression status was available, 56% had tumors of high expression; 26%, medium expression; and 18%, low expression. In the control group, Trop-2 expression was known in 139 patients, of whom 52% had tumors of high expression; 25%, medium expression; and 23%, low expression.
Hurvitz reported that, although median PFS among patients given SG decreased with decreasing Trop-2 expression, it remained longer than that seen with control treatment. In patients with tumors of Trop-2–high status, median PFS was 6.9 months with SG, vs. 2.5 for patients who underwent control treatment. This fell to 5.6 months vs. 2.2 months in the Trop-2–medium group and 2.7 months vs 1.6 months in Trop-2–low group.
A similar pattern was seen for overall survival. In the Trop-2–high group, median overall survival was 14.2 months with SG, vs. 6.9 months with control therapy; 14.9 months vs. 6.9 months in the Trop-2–medium group; and 9.3 months vs. 7.6 months in the Trop-2–low group.
Again, the objective response rate fell from 44% to 38% and then to 22% with SG in the Trop-2–high, –medium, and –low groups, compared with 1%, 11%, and 6%, respectively, with control treatment.
There did not seem to be any interaction between Trop-2 expression and treatment-related adverse events of special interest. Rates of neutropenia, diarrhea, and anemia were consistently higher in SG-treated patients than in those given placebo.
Hurvitz said the objective response rate was markedly higher with SG vs. control treatment in both BRCA1/2-positive and -negative patients, at 19% vs. 6% in the positive group and 33% vs. 6% in the negative group.
This was reflected in improved median PFS with SG in both subgroups, at 4.6 months vs. 2.5 months with control therapy in BRCA1/2-positive patients and 4.9 months vs. 1.6 months in BRCA1/2-negative patients.
Overall survival was 15.6 months with SG, vs. 4.4 months with control treatment in BRCA1/2-positive patients. In BRCA1/2-negative patients, the respective figures were 10.9 months and 7.0 months.
The study was sponsored by Immunomedics. Hurvitz has financial ties to Immunomedics and multiple other pharmaceutical companies. Litton has financial ties to multiple companies, including Medscape and companies developing and marketing breast cancer therapies.
This article first appeared on Medscape.com.
FROM SABCS 2020
Adding atezolizumab to chemo doesn’t worsen QOL in early TNBC
In the randomized phase 3 trial, patients received neoadjuvant atezolizumab or placebo plus chemotherapy, followed by surgery and adjuvant atezolizumab or observation.
An analysis of patient-reported outcomes showed that, after a brief decline in health-related quality of life (HRQOL) in both the atezolizumab and control arms, the burden of treatment eased and then remained similar throughout follow-up.
“Treatment-related symptoms in both arms were similar, and the addition of atezolizumab to chemotherapy was tolerable, with no additional treatment side-effect bother reported,” said Elizabeth Mittendorf, MD, PhD, of the Dana-Farber Cancer Institute in Boston.
She presented these results in an oral abstract presentation during the 2020 San Antonio Breast Cancer Symposium.
Initial results
Primary results of the IMpassion031 trial were reported at ESMO 2020 and published in The Lancet.
The trial enrolled patients with treatment-naive early TNBC, and they were randomized to receive chemotherapy plus atezolizumab or placebo. Atezolizumab was given at 840 mg intravenously every 2 weeks.
Chemotherapy consisted of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks. Patients then underwent surgery, which was followed by either atezolizumab maintenance or observation.
The addition of atezolizumab was associated with a 17% improvement in the rate of pathological complete response (pCR) in the intention-to-treat population.
Among patients positive for PD-L1, atezolizumab was associated with a 20% improvement in pCR rate.
Patients have their say
At SABCS 2020, Dr. Mittendorf presented patient-reported outcomes (PRO) for 161 patients randomized to atezolizumab plus chemotherapy and 167 assigned to placebo plus chemotherapy.
The outcome measures – including role function (the ability to work or pursue common everyday activities), physical function, emotional and social function, and HRQOL – came from scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
The exploratory PRO endpoints were mean function and disease- or treatment-related symptoms as well as mean change from baseline in these symptoms.
At baseline, mean physical function scores were high in both arms, at approximately 90%. They dropped to about 65% in each arm by cycle 5 and rebounded to about 80% by cycle 7.
“The change was clinically meaningful, in that the dip was greater than 10 points,” Dr. Mittendorf said. “As patients completed neoadjuvant therapy and were in the adjuvant phase of the study, there was an increase and stabilization with respect to their physical function.”
Similarly, role function declined from 89% in each arm at baseline to a nadir of about 55% in the placebo arm and 50% in the atezolizumab arm. After cycle 5, role function levels began to increase in both arms and remained above 70% from cycle 7 onward.
Role function did not completely recover or stabilize among patients in the atezolizumab arm, “and we attribute this to the fact that these patients continue to receive atezolizumab, which requires that they come to clinic for that therapy, thereby potentially impacting role function,” Dr. Mittendorf said.
She reported that HRQOL declined from a median of nearly 80% at baseline in both arms to a nadir of 62% in the placebo arm and 52% in the atezolizumab arm by cycle 5. HRQOL rebounded starting at cycle 6 and stabilized thereafter, with little daylight between the treatment arms at the most recent follow-up.
The investigators saw worsening of the treatment-related symptoms fatigue, nausea/vomiting, and diarrhea in each arm, with the highest level of symptoms except pain reported at cycle 5. The highest reported pain level was seen at cycle 4.
In each arm, the symptoms declined and stabilized in the adjuvant setting, with mean values at week 16 similar to those reported at baseline for most symptoms. The exception was fatigue, which remained slightly elevated in both arms.
Regarding side-effect bother, a similar proportion of patients in each arm reported increased level of bother by visit during the neoadjuvant phase. However, no additional side-effect bother was reported by patients receiving maintenance atezolizumab, compared with patients in the placebo arm, who were followed with observation alone.
‘Reassuring’ data
“What we can conclude from the PRO in IMpassion031 is that early breast cancer patients are relatively asymptomatic. They do have a good baseline quality of life and very good functioning. The neoadjuvant therapy certainly has deterioration in quality of life and functioning, but this is transient, and there was no evident burden from the atezolizumab,” said invited discussant Sylvia Adams, MD, of New York University.
She said it’s reassuring to see the addition of atezolizumab did not adversely affect HRQOL but added that the study “also shows that chemotherapy has a major impact on well-being, as expected.”
Questions and problems that still need to be addressed regarding the use of immunotherapies in early TNBC include whether every patient needs chemotherapy or immunotherapy, a lack of predictive biomarkers, whether increases in pCR rates after neoadjuvant immunotherapy and chemotherapy will translate into improved survival, and the optimal chemotherapy backbone and schedule, she said.
IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly. Dr. Adams disclosed relationships with Genentech, Bristol Myers Squibb, Merck, Amgen, Celgene, and Novartis.
SOURCE: Mittendorf E at al. SABCS 2020, Abstract GS3-02.
In the randomized phase 3 trial, patients received neoadjuvant atezolizumab or placebo plus chemotherapy, followed by surgery and adjuvant atezolizumab or observation.
An analysis of patient-reported outcomes showed that, after a brief decline in health-related quality of life (HRQOL) in both the atezolizumab and control arms, the burden of treatment eased and then remained similar throughout follow-up.
“Treatment-related symptoms in both arms were similar, and the addition of atezolizumab to chemotherapy was tolerable, with no additional treatment side-effect bother reported,” said Elizabeth Mittendorf, MD, PhD, of the Dana-Farber Cancer Institute in Boston.
She presented these results in an oral abstract presentation during the 2020 San Antonio Breast Cancer Symposium.
Initial results
Primary results of the IMpassion031 trial were reported at ESMO 2020 and published in The Lancet.
The trial enrolled patients with treatment-naive early TNBC, and they were randomized to receive chemotherapy plus atezolizumab or placebo. Atezolizumab was given at 840 mg intravenously every 2 weeks.
Chemotherapy consisted of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks. Patients then underwent surgery, which was followed by either atezolizumab maintenance or observation.
The addition of atezolizumab was associated with a 17% improvement in the rate of pathological complete response (pCR) in the intention-to-treat population.
Among patients positive for PD-L1, atezolizumab was associated with a 20% improvement in pCR rate.
Patients have their say
At SABCS 2020, Dr. Mittendorf presented patient-reported outcomes (PRO) for 161 patients randomized to atezolizumab plus chemotherapy and 167 assigned to placebo plus chemotherapy.
The outcome measures – including role function (the ability to work or pursue common everyday activities), physical function, emotional and social function, and HRQOL – came from scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
The exploratory PRO endpoints were mean function and disease- or treatment-related symptoms as well as mean change from baseline in these symptoms.
At baseline, mean physical function scores were high in both arms, at approximately 90%. They dropped to about 65% in each arm by cycle 5 and rebounded to about 80% by cycle 7.
“The change was clinically meaningful, in that the dip was greater than 10 points,” Dr. Mittendorf said. “As patients completed neoadjuvant therapy and were in the adjuvant phase of the study, there was an increase and stabilization with respect to their physical function.”
Similarly, role function declined from 89% in each arm at baseline to a nadir of about 55% in the placebo arm and 50% in the atezolizumab arm. After cycle 5, role function levels began to increase in both arms and remained above 70% from cycle 7 onward.
Role function did not completely recover or stabilize among patients in the atezolizumab arm, “and we attribute this to the fact that these patients continue to receive atezolizumab, which requires that they come to clinic for that therapy, thereby potentially impacting role function,” Dr. Mittendorf said.
She reported that HRQOL declined from a median of nearly 80% at baseline in both arms to a nadir of 62% in the placebo arm and 52% in the atezolizumab arm by cycle 5. HRQOL rebounded starting at cycle 6 and stabilized thereafter, with little daylight between the treatment arms at the most recent follow-up.
The investigators saw worsening of the treatment-related symptoms fatigue, nausea/vomiting, and diarrhea in each arm, with the highest level of symptoms except pain reported at cycle 5. The highest reported pain level was seen at cycle 4.
In each arm, the symptoms declined and stabilized in the adjuvant setting, with mean values at week 16 similar to those reported at baseline for most symptoms. The exception was fatigue, which remained slightly elevated in both arms.
Regarding side-effect bother, a similar proportion of patients in each arm reported increased level of bother by visit during the neoadjuvant phase. However, no additional side-effect bother was reported by patients receiving maintenance atezolizumab, compared with patients in the placebo arm, who were followed with observation alone.
‘Reassuring’ data
“What we can conclude from the PRO in IMpassion031 is that early breast cancer patients are relatively asymptomatic. They do have a good baseline quality of life and very good functioning. The neoadjuvant therapy certainly has deterioration in quality of life and functioning, but this is transient, and there was no evident burden from the atezolizumab,” said invited discussant Sylvia Adams, MD, of New York University.
She said it’s reassuring to see the addition of atezolizumab did not adversely affect HRQOL but added that the study “also shows that chemotherapy has a major impact on well-being, as expected.”
Questions and problems that still need to be addressed regarding the use of immunotherapies in early TNBC include whether every patient needs chemotherapy or immunotherapy, a lack of predictive biomarkers, whether increases in pCR rates after neoadjuvant immunotherapy and chemotherapy will translate into improved survival, and the optimal chemotherapy backbone and schedule, she said.
IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly. Dr. Adams disclosed relationships with Genentech, Bristol Myers Squibb, Merck, Amgen, Celgene, and Novartis.
SOURCE: Mittendorf E at al. SABCS 2020, Abstract GS3-02.
In the randomized phase 3 trial, patients received neoadjuvant atezolizumab or placebo plus chemotherapy, followed by surgery and adjuvant atezolizumab or observation.
An analysis of patient-reported outcomes showed that, after a brief decline in health-related quality of life (HRQOL) in both the atezolizumab and control arms, the burden of treatment eased and then remained similar throughout follow-up.
“Treatment-related symptoms in both arms were similar, and the addition of atezolizumab to chemotherapy was tolerable, with no additional treatment side-effect bother reported,” said Elizabeth Mittendorf, MD, PhD, of the Dana-Farber Cancer Institute in Boston.
She presented these results in an oral abstract presentation during the 2020 San Antonio Breast Cancer Symposium.
Initial results
Primary results of the IMpassion031 trial were reported at ESMO 2020 and published in The Lancet.
The trial enrolled patients with treatment-naive early TNBC, and they were randomized to receive chemotherapy plus atezolizumab or placebo. Atezolizumab was given at 840 mg intravenously every 2 weeks.
Chemotherapy consisted of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks. Patients then underwent surgery, which was followed by either atezolizumab maintenance or observation.
The addition of atezolizumab was associated with a 17% improvement in the rate of pathological complete response (pCR) in the intention-to-treat population.
Among patients positive for PD-L1, atezolizumab was associated with a 20% improvement in pCR rate.
Patients have their say
At SABCS 2020, Dr. Mittendorf presented patient-reported outcomes (PRO) for 161 patients randomized to atezolizumab plus chemotherapy and 167 assigned to placebo plus chemotherapy.
The outcome measures – including role function (the ability to work or pursue common everyday activities), physical function, emotional and social function, and HRQOL – came from scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
The exploratory PRO endpoints were mean function and disease- or treatment-related symptoms as well as mean change from baseline in these symptoms.
At baseline, mean physical function scores were high in both arms, at approximately 90%. They dropped to about 65% in each arm by cycle 5 and rebounded to about 80% by cycle 7.
“The change was clinically meaningful, in that the dip was greater than 10 points,” Dr. Mittendorf said. “As patients completed neoadjuvant therapy and were in the adjuvant phase of the study, there was an increase and stabilization with respect to their physical function.”
Similarly, role function declined from 89% in each arm at baseline to a nadir of about 55% in the placebo arm and 50% in the atezolizumab arm. After cycle 5, role function levels began to increase in both arms and remained above 70% from cycle 7 onward.
Role function did not completely recover or stabilize among patients in the atezolizumab arm, “and we attribute this to the fact that these patients continue to receive atezolizumab, which requires that they come to clinic for that therapy, thereby potentially impacting role function,” Dr. Mittendorf said.
She reported that HRQOL declined from a median of nearly 80% at baseline in both arms to a nadir of 62% in the placebo arm and 52% in the atezolizumab arm by cycle 5. HRQOL rebounded starting at cycle 6 and stabilized thereafter, with little daylight between the treatment arms at the most recent follow-up.
The investigators saw worsening of the treatment-related symptoms fatigue, nausea/vomiting, and diarrhea in each arm, with the highest level of symptoms except pain reported at cycle 5. The highest reported pain level was seen at cycle 4.
In each arm, the symptoms declined and stabilized in the adjuvant setting, with mean values at week 16 similar to those reported at baseline for most symptoms. The exception was fatigue, which remained slightly elevated in both arms.
Regarding side-effect bother, a similar proportion of patients in each arm reported increased level of bother by visit during the neoadjuvant phase. However, no additional side-effect bother was reported by patients receiving maintenance atezolizumab, compared with patients in the placebo arm, who were followed with observation alone.
‘Reassuring’ data
“What we can conclude from the PRO in IMpassion031 is that early breast cancer patients are relatively asymptomatic. They do have a good baseline quality of life and very good functioning. The neoadjuvant therapy certainly has deterioration in quality of life and functioning, but this is transient, and there was no evident burden from the atezolizumab,” said invited discussant Sylvia Adams, MD, of New York University.
She said it’s reassuring to see the addition of atezolizumab did not adversely affect HRQOL but added that the study “also shows that chemotherapy has a major impact on well-being, as expected.”
Questions and problems that still need to be addressed regarding the use of immunotherapies in early TNBC include whether every patient needs chemotherapy or immunotherapy, a lack of predictive biomarkers, whether increases in pCR rates after neoadjuvant immunotherapy and chemotherapy will translate into improved survival, and the optimal chemotherapy backbone and schedule, she said.
IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly. Dr. Adams disclosed relationships with Genentech, Bristol Myers Squibb, Merck, Amgen, Celgene, and Novartis.
SOURCE: Mittendorf E at al. SABCS 2020, Abstract GS3-02.
FROM SABCS 2020
Pregnancy after breast cancer is rockier but doesn’t increase recurrence risk
Breast cancer survivors are less likely to get pregnant and have higher risks of some delivery and fetal complications, according to a meta-analysis reported at the 2020 San Antonio Breast Cancer Symposium.
However, the data also showed that pregnancy does not increase the risk of cancer recurrence.
“With the availability of more effective anticancer treatments, survivorship and addressing the treatments’ potential long-term toxicities has gained substantial attention,” said study investigator Matteo Lambertini, MD, PhD, of University of Genova (Italy) – IRCCS Policlinico San Martino Hospital.
“Returning to a normal life after cancer diagnosis and treatment should be considered, in the 21st century, as a crucial ambition in cancer care,” Dr. Lambertini added. “In patients diagnosed during their reproductive years, this includes the possibility to complete their family planning. Due to the constant rise in age at first pregnancy over the past years, many women are diagnosed with breast cancer before completing their reproductive plans.”
In that context, certain cancer treatments have the potential to reduce fertility. In addition, many women need prolonged hormone therapy, and conception is contraindicated while they are receiving it.
Study results
Dr. Lambertini and colleagues performed a meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.
Results showed that breast cancer survivors were much less likely than women in the general population to become pregnant (relative risk, 0.40; P < .001).
However, “the majority of the studies included in our meta-analysis did not capture the information on how many women tried to get pregnant,” Dr. Lambertini cautioned.
In the few studies that did, more than half of women trying to conceive did become pregnant, and most of them were able to do so naturally, without need for assisted reproductive technologies.
On the flip side, analyses also showed that pregnancies occurred in some women who did not want to conceive, underscoring the importance of comprehensive oncofertility counseling that addresses not only fertility preservation, but also contraception, Dr. Lambertini said.
Among women who became pregnant, breast cancer survivors did not have higher odds of spontaneous abortion or complications such as preeclampsia, and their infants were not significantly more likely to have congenital abnormalities.
However, the breast cancer survivor group did have higher odds of cesarean birth (odds ratio, 1.14; P = .007), low birth weight (OR, 1.50; P < .001), preterm birth (OR, 1.45; P = .006), and infants small for gestational age (OR, 1.16; P = .039).
In stratified analysis, the higher risk of having an infant with low birth weight was significant only for women who had received chemotherapy, and the higher risk of having an infant small for gestational age was significant only for women who had received chemotherapy or who had a late pregnancy (more than 2 years to 5 years after cancer diagnosis).
Among breast cancer survivors, those who became pregnant actually had lower risks of disease-free survival events (hazard ratio, 0.73; P = .016) and death (HR, 0.56; P < .001). Findings were similar in the subset of studies that adjusted for the so-called healthy mother effect.
Pregnancy did not significantly affect disease-free survival among women with hormone receptor–positive disease and appeared protective among women with hormone receptor–negative disease (HR, 0.72).
Pregnancy also appeared safe in terms of overall survival, irrespective of survivors’ BRCA status, nodal status, receipt of chemotherapy, pregnancy outcome (completed vs. abortion), and pregnancy interval.
This study was limited by the lack of patient-level data and by the fact that most of the included studies had a retrospective design, Dr. Lambertini acknowledged.
Close monitoring, early discussions are key
“Results of this meta-analysis provide reassuring, updated evidence on the feasibility and safety of conceiving in young women with prior breast cancer diagnosis. They provide crucial information for improving the oncofertility counseling of young breast cancer patients, helping them and their treating physicians in making evidence-based decisions on future family planning,” Dr. Lambertini commented.
“The higher risk of delivery and fetal complications … calls for ensuring a closer monitoring of these pregnancies,” he added. “The lack of detrimental prognostic effect of pregnancy after breast cancer following appropriate treatment and follow-up strongly voices the need for a deeper consideration of patients’ pregnancy desire as a crucial component of their survivorship care plan and wish to return to a normal life.”
“The findings provide further support regarding the safety of pregnancy following a breast cancer diagnosis,” agreed Halle Moore, MD, of Cleveland Clinic Taussig Cancer Institute in Ohio, who was not involved in this study.
“I would add that we still have a lot to learn about optimal timing of pregnancy with respect to breast cancer treatment for women with hormone-sensitive breast cancer treated with endocrine therapy,” she said.
The study’s results serve as a reminder that providers should be routinely discussing future pregnancy wishes and fertility preservation options with breast cancer patients at the time of initial diagnosis, Dr. Moore said.
“The earlier we identify an interest in future fertility, the more we can do to improve the chances for a successful pregnancy outcome,” she elaborated. “It is important to assess interest in future pregnancy as soon as possible when a young woman is diagnosed with breast cancer, as fertility preservation options are most likely to be successful when applied prior to chemotherapy or hormonal treatment for breast cancer.”
“The findings also suggest that involvement of a high-risk obstetrics team should be considered for pregnant breast cancer survivors,” Dr. Moore noted.
This research was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Lambertini and Dr. Moore disclosed no conflicts of interest. Eva Blondeaux, MD, of University of Genova – IRCCS Policlinico San Martino Hospital, who presented this research at the meeting, disclosed no conflicts as well.
SOURCE: Blondeaux e et al. SABCS 2020, Abstract GS3-09.
Breast cancer survivors are less likely to get pregnant and have higher risks of some delivery and fetal complications, according to a meta-analysis reported at the 2020 San Antonio Breast Cancer Symposium.
However, the data also showed that pregnancy does not increase the risk of cancer recurrence.
“With the availability of more effective anticancer treatments, survivorship and addressing the treatments’ potential long-term toxicities has gained substantial attention,” said study investigator Matteo Lambertini, MD, PhD, of University of Genova (Italy) – IRCCS Policlinico San Martino Hospital.
“Returning to a normal life after cancer diagnosis and treatment should be considered, in the 21st century, as a crucial ambition in cancer care,” Dr. Lambertini added. “In patients diagnosed during their reproductive years, this includes the possibility to complete their family planning. Due to the constant rise in age at first pregnancy over the past years, many women are diagnosed with breast cancer before completing their reproductive plans.”
In that context, certain cancer treatments have the potential to reduce fertility. In addition, many women need prolonged hormone therapy, and conception is contraindicated while they are receiving it.
Study results
Dr. Lambertini and colleagues performed a meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.
Results showed that breast cancer survivors were much less likely than women in the general population to become pregnant (relative risk, 0.40; P < .001).
However, “the majority of the studies included in our meta-analysis did not capture the information on how many women tried to get pregnant,” Dr. Lambertini cautioned.
In the few studies that did, more than half of women trying to conceive did become pregnant, and most of them were able to do so naturally, without need for assisted reproductive technologies.
On the flip side, analyses also showed that pregnancies occurred in some women who did not want to conceive, underscoring the importance of comprehensive oncofertility counseling that addresses not only fertility preservation, but also contraception, Dr. Lambertini said.
Among women who became pregnant, breast cancer survivors did not have higher odds of spontaneous abortion or complications such as preeclampsia, and their infants were not significantly more likely to have congenital abnormalities.
However, the breast cancer survivor group did have higher odds of cesarean birth (odds ratio, 1.14; P = .007), low birth weight (OR, 1.50; P < .001), preterm birth (OR, 1.45; P = .006), and infants small for gestational age (OR, 1.16; P = .039).
In stratified analysis, the higher risk of having an infant with low birth weight was significant only for women who had received chemotherapy, and the higher risk of having an infant small for gestational age was significant only for women who had received chemotherapy or who had a late pregnancy (more than 2 years to 5 years after cancer diagnosis).
Among breast cancer survivors, those who became pregnant actually had lower risks of disease-free survival events (hazard ratio, 0.73; P = .016) and death (HR, 0.56; P < .001). Findings were similar in the subset of studies that adjusted for the so-called healthy mother effect.
Pregnancy did not significantly affect disease-free survival among women with hormone receptor–positive disease and appeared protective among women with hormone receptor–negative disease (HR, 0.72).
Pregnancy also appeared safe in terms of overall survival, irrespective of survivors’ BRCA status, nodal status, receipt of chemotherapy, pregnancy outcome (completed vs. abortion), and pregnancy interval.
This study was limited by the lack of patient-level data and by the fact that most of the included studies had a retrospective design, Dr. Lambertini acknowledged.
Close monitoring, early discussions are key
“Results of this meta-analysis provide reassuring, updated evidence on the feasibility and safety of conceiving in young women with prior breast cancer diagnosis. They provide crucial information for improving the oncofertility counseling of young breast cancer patients, helping them and their treating physicians in making evidence-based decisions on future family planning,” Dr. Lambertini commented.
“The higher risk of delivery and fetal complications … calls for ensuring a closer monitoring of these pregnancies,” he added. “The lack of detrimental prognostic effect of pregnancy after breast cancer following appropriate treatment and follow-up strongly voices the need for a deeper consideration of patients’ pregnancy desire as a crucial component of their survivorship care plan and wish to return to a normal life.”
“The findings provide further support regarding the safety of pregnancy following a breast cancer diagnosis,” agreed Halle Moore, MD, of Cleveland Clinic Taussig Cancer Institute in Ohio, who was not involved in this study.
“I would add that we still have a lot to learn about optimal timing of pregnancy with respect to breast cancer treatment for women with hormone-sensitive breast cancer treated with endocrine therapy,” she said.
The study’s results serve as a reminder that providers should be routinely discussing future pregnancy wishes and fertility preservation options with breast cancer patients at the time of initial diagnosis, Dr. Moore said.
“The earlier we identify an interest in future fertility, the more we can do to improve the chances for a successful pregnancy outcome,” she elaborated. “It is important to assess interest in future pregnancy as soon as possible when a young woman is diagnosed with breast cancer, as fertility preservation options are most likely to be successful when applied prior to chemotherapy or hormonal treatment for breast cancer.”
“The findings also suggest that involvement of a high-risk obstetrics team should be considered for pregnant breast cancer survivors,” Dr. Moore noted.
This research was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Lambertini and Dr. Moore disclosed no conflicts of interest. Eva Blondeaux, MD, of University of Genova – IRCCS Policlinico San Martino Hospital, who presented this research at the meeting, disclosed no conflicts as well.
SOURCE: Blondeaux e et al. SABCS 2020, Abstract GS3-09.
Breast cancer survivors are less likely to get pregnant and have higher risks of some delivery and fetal complications, according to a meta-analysis reported at the 2020 San Antonio Breast Cancer Symposium.
However, the data also showed that pregnancy does not increase the risk of cancer recurrence.
“With the availability of more effective anticancer treatments, survivorship and addressing the treatments’ potential long-term toxicities has gained substantial attention,” said study investigator Matteo Lambertini, MD, PhD, of University of Genova (Italy) – IRCCS Policlinico San Martino Hospital.
“Returning to a normal life after cancer diagnosis and treatment should be considered, in the 21st century, as a crucial ambition in cancer care,” Dr. Lambertini added. “In patients diagnosed during their reproductive years, this includes the possibility to complete their family planning. Due to the constant rise in age at first pregnancy over the past years, many women are diagnosed with breast cancer before completing their reproductive plans.”
In that context, certain cancer treatments have the potential to reduce fertility. In addition, many women need prolonged hormone therapy, and conception is contraindicated while they are receiving it.
Study results
Dr. Lambertini and colleagues performed a meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.
Results showed that breast cancer survivors were much less likely than women in the general population to become pregnant (relative risk, 0.40; P < .001).
However, “the majority of the studies included in our meta-analysis did not capture the information on how many women tried to get pregnant,” Dr. Lambertini cautioned.
In the few studies that did, more than half of women trying to conceive did become pregnant, and most of them were able to do so naturally, without need for assisted reproductive technologies.
On the flip side, analyses also showed that pregnancies occurred in some women who did not want to conceive, underscoring the importance of comprehensive oncofertility counseling that addresses not only fertility preservation, but also contraception, Dr. Lambertini said.
Among women who became pregnant, breast cancer survivors did not have higher odds of spontaneous abortion or complications such as preeclampsia, and their infants were not significantly more likely to have congenital abnormalities.
However, the breast cancer survivor group did have higher odds of cesarean birth (odds ratio, 1.14; P = .007), low birth weight (OR, 1.50; P < .001), preterm birth (OR, 1.45; P = .006), and infants small for gestational age (OR, 1.16; P = .039).
In stratified analysis, the higher risk of having an infant with low birth weight was significant only for women who had received chemotherapy, and the higher risk of having an infant small for gestational age was significant only for women who had received chemotherapy or who had a late pregnancy (more than 2 years to 5 years after cancer diagnosis).
Among breast cancer survivors, those who became pregnant actually had lower risks of disease-free survival events (hazard ratio, 0.73; P = .016) and death (HR, 0.56; P < .001). Findings were similar in the subset of studies that adjusted for the so-called healthy mother effect.
Pregnancy did not significantly affect disease-free survival among women with hormone receptor–positive disease and appeared protective among women with hormone receptor–negative disease (HR, 0.72).
Pregnancy also appeared safe in terms of overall survival, irrespective of survivors’ BRCA status, nodal status, receipt of chemotherapy, pregnancy outcome (completed vs. abortion), and pregnancy interval.
This study was limited by the lack of patient-level data and by the fact that most of the included studies had a retrospective design, Dr. Lambertini acknowledged.
Close monitoring, early discussions are key
“Results of this meta-analysis provide reassuring, updated evidence on the feasibility and safety of conceiving in young women with prior breast cancer diagnosis. They provide crucial information for improving the oncofertility counseling of young breast cancer patients, helping them and their treating physicians in making evidence-based decisions on future family planning,” Dr. Lambertini commented.
“The higher risk of delivery and fetal complications … calls for ensuring a closer monitoring of these pregnancies,” he added. “The lack of detrimental prognostic effect of pregnancy after breast cancer following appropriate treatment and follow-up strongly voices the need for a deeper consideration of patients’ pregnancy desire as a crucial component of their survivorship care plan and wish to return to a normal life.”
“The findings provide further support regarding the safety of pregnancy following a breast cancer diagnosis,” agreed Halle Moore, MD, of Cleveland Clinic Taussig Cancer Institute in Ohio, who was not involved in this study.
“I would add that we still have a lot to learn about optimal timing of pregnancy with respect to breast cancer treatment for women with hormone-sensitive breast cancer treated with endocrine therapy,” she said.
The study’s results serve as a reminder that providers should be routinely discussing future pregnancy wishes and fertility preservation options with breast cancer patients at the time of initial diagnosis, Dr. Moore said.
“The earlier we identify an interest in future fertility, the more we can do to improve the chances for a successful pregnancy outcome,” she elaborated. “It is important to assess interest in future pregnancy as soon as possible when a young woman is diagnosed with breast cancer, as fertility preservation options are most likely to be successful when applied prior to chemotherapy or hormonal treatment for breast cancer.”
“The findings also suggest that involvement of a high-risk obstetrics team should be considered for pregnant breast cancer survivors,” Dr. Moore noted.
This research was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Lambertini and Dr. Moore disclosed no conflicts of interest. Eva Blondeaux, MD, of University of Genova – IRCCS Policlinico San Martino Hospital, who presented this research at the meeting, disclosed no conflicts as well.
SOURCE: Blondeaux e et al. SABCS 2020, Abstract GS3-09.
FROM SABCS 2020
RxPONDER: Even more women may forgo chemo for breast cancer
More women with early-stage breast cancer may safely forgo chemotherapy, suggests an interim analysis of the large-scale phase 3 RxPONDER trial, presented at the San Antonio Breast Cancer Symposium 2020.
The investigators reported that adding chemotherapy to endocrine therapy did not improve outcomes for postmenopausal women with low-risk, node-positive, hormone receptor–positive (HR+), HER2-negative (HER2–) breast cancer in comparison with endocrine therapy alone.
These results are akin to those from the TAILORx trial. The results of that trial were first presented in 2018 and have changed practice for women with early-stage disease who have no lymph node involvement.
Clinicians celebrated the new results for women with lymph node–positive disease.
“RxPonder: practice changing!!!” tweeted meeting attendee Sarah Sammons, MD, Duke Cancer Center, Durham, N.C.
“Data from RxPonder are the most clinically important this year at @SABCSSanAntonio,” tweeted Hal Burstein, MD, Dana Farber Cancer Institute, Boston, who was not involved in the study.
“This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions,” asserted study lead author Kevin Kalinsky, MD, Winship Cancer Institute of Emory University, Atlanta, during a meeting press conference.
But the trial, run by the SWOG Cancer Research Network, was not without controversy.
That’s because the trial also included premenopausal women whose disease characteristics were the same and who were found to have benefited from chemotherapy.
It was not clear whether the benefit was from chemotherapy’s cytotoxicity or its endocrine effects/ovarian suppression (which limits the production of estrogen, a breast cell stimulant) in these young women. But multiple experts asserted that the effect was very likely from ovarian suppression.
“There are less toxic ways than chemo to suppress ovarian function,” tweeted Tatiana Prowell, MD, Johns Hopkins University, Baltimore, who is not a study investigator.
Some experts strongly doubted the findings in premenopausal women.
“I hate to come away with the message that all [low-risk, node-positive] premenopausal patients should get chemotherapy,” summarized C. Kent Osborne, MD, Baylor College of Medicine, Houston, who is codirector of SABCS and was not involved in the study.
RxPONDER will follow patients for 15 years, so additional data and insights will follow, observed SWOG in a press statement.
Women had limited positive nodes
RxPONDER, or SWOG S1007, involved more than 5000 women who had HR+, HER2– breast cancer with involvement of one to three lymph nodes. The patients’ recurrence score was ≤25 on a 21-tumor gene expression assay (Oncotype Dx), which is characterized as low risk.
Approximately 20% of U.S. women with nonmetastatic HR+, HER2– breast cancer present with involvement of one to three lymph nodes, Dr. Kalinsky noted.
Study participants were randomly assigned to receive either standard chemotherapy plus endocrine therapy or endocrine therapy alone. Follow-up was for a median of 5 years before the current preplanned analysis.
Over a median follow-up of 5.1 years, there were 447 observed invasive disease-free survival (IDFS) events, the primary endpoint, which is 54% of the expected number at final analysis.
Across the whole cohort, adding chemotherapy to endocrine therapy was associated with a significant improvement in IDFS, with a 5-year rate of 92.4% vs 91.0% for endocrine therapy (P = .026).
Among the postmenopausal women, no such improvement was seen. The 5-year IDFS rate was 91.6% with chemotherapy plus endocrine therapy and 91.9% with endocrine therapy alone (P = .82).
Among premenopausal women, there was improvement in IDFS. The 5-year rate was 94.2% with chemotherapy plus endocrine therapy and 89.0% for endocrine therapy alone (P = .0004).
These differences were reflected in the results for overall survival. For postmenopausal women, there was a nonsignificant difference in 5-year overall survival rates (96.2% vs. 96.1%).
On the other hand, for premenopausal women, there was a significant difference in 5-year overall survival rates (98.6% vs. 97.3%; P = .032).
Stratifying patients by recurrence score, 0-13 versus 14-25, and by involvement of one versus two to three nodes did not have a major impact on the results, said Dr. Kalinsky, who also noted that future analyses will include quality of life and other outcomes.
More about endocrine therapy in RxPONDER
Dr. Osborne said that premenopausal women in RxPONDER were “nearly always” prescribed tamoxifen.
However, he observed that the current standard approach to treatment in this age group would be ovarian suppression plus either an aromatase inhibitor or tamoxifen, “both of which have been shown to be superior to tamoxifen alone in this subgroup.
“Since the adjuvant chemotherapy causes ovarian suppression in many premenopausal patients,” he said, “these patients then, in fact, received ovarian suppression plus tamoxifen,” rather than tamoxifen alone for the group that did not receive chemotherapy.
Dr. Osborne asked a question that came up again and again during the postpresentation discussion: “Is the difference in outcome in this subset due to the endocrine effects of chemotherapy? Unfortunately, we may never know the answer to this question,” he said.
Dr. Kalinsky replied that whether the difference in benefit of chemotherapy in premenopausal women “was a direct benefit, meaning that there’s something about the biology difference” between tumors in premenopausal versus postmenopausal women, “or whether this was an indirect effect, meaning impacting rates of amenorrhea... is not specifically how this study was designed.”
However, an exploratory landmark analysis at 6 months suggested that the use of ovarian suppression with endocrine therapy did not have an effect on outcomes.
Dr. Osborne said he is nevertheless “still skeptical that chemotherapy works differently in premenopausal women. Until we show that it’s not an endocrine effect ... I just can’t imagine why that group of patients, even the ones with very low Oncotype [score], would have a different response to chemotherapy.”
He added: “If I can think of a rationale ... I would believe it, but right now, I’m a little bit skeptical.”
Virginia Kaklamani, MD, of the University of Texas Health San Antonio Cancer Center, San Antonio, who is a meeting codirector, said she wanted to “second that.
“I honestly think that this is an OFS [ovarian function suppression effect] that we are seeing. We have several clinical trials that have been done looking at ovarian function suppression versus not ... showing that [it] can help as much as chemotherapy.”
Dr. Kaklamani continued: “Unfortunately, the arms to those trials were not perfect for now, and this is going to be an unanswered question until we have a large trial comparing OFS to chemotherapy.”
The study was sponsored by the National Cancer Institute, the Susan G. Komen for the Cure Research Program, the Hope Foundation for Cancer Research, the Breast Cancer Research Foundation, and Exact Sciences. Dr. Kalinsky, Dr. Osborne, and Dr. Kaklamani report financial ties to multiple pharmaceutical companies.
This article first appeared on Medscape.com.
More women with early-stage breast cancer may safely forgo chemotherapy, suggests an interim analysis of the large-scale phase 3 RxPONDER trial, presented at the San Antonio Breast Cancer Symposium 2020.
The investigators reported that adding chemotherapy to endocrine therapy did not improve outcomes for postmenopausal women with low-risk, node-positive, hormone receptor–positive (HR+), HER2-negative (HER2–) breast cancer in comparison with endocrine therapy alone.
These results are akin to those from the TAILORx trial. The results of that trial were first presented in 2018 and have changed practice for women with early-stage disease who have no lymph node involvement.
Clinicians celebrated the new results for women with lymph node–positive disease.
“RxPonder: practice changing!!!” tweeted meeting attendee Sarah Sammons, MD, Duke Cancer Center, Durham, N.C.
“Data from RxPonder are the most clinically important this year at @SABCSSanAntonio,” tweeted Hal Burstein, MD, Dana Farber Cancer Institute, Boston, who was not involved in the study.
“This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions,” asserted study lead author Kevin Kalinsky, MD, Winship Cancer Institute of Emory University, Atlanta, during a meeting press conference.
But the trial, run by the SWOG Cancer Research Network, was not without controversy.
That’s because the trial also included premenopausal women whose disease characteristics were the same and who were found to have benefited from chemotherapy.
It was not clear whether the benefit was from chemotherapy’s cytotoxicity or its endocrine effects/ovarian suppression (which limits the production of estrogen, a breast cell stimulant) in these young women. But multiple experts asserted that the effect was very likely from ovarian suppression.
“There are less toxic ways than chemo to suppress ovarian function,” tweeted Tatiana Prowell, MD, Johns Hopkins University, Baltimore, who is not a study investigator.
Some experts strongly doubted the findings in premenopausal women.
“I hate to come away with the message that all [low-risk, node-positive] premenopausal patients should get chemotherapy,” summarized C. Kent Osborne, MD, Baylor College of Medicine, Houston, who is codirector of SABCS and was not involved in the study.
RxPONDER will follow patients for 15 years, so additional data and insights will follow, observed SWOG in a press statement.
Women had limited positive nodes
RxPONDER, or SWOG S1007, involved more than 5000 women who had HR+, HER2– breast cancer with involvement of one to three lymph nodes. The patients’ recurrence score was ≤25 on a 21-tumor gene expression assay (Oncotype Dx), which is characterized as low risk.
Approximately 20% of U.S. women with nonmetastatic HR+, HER2– breast cancer present with involvement of one to three lymph nodes, Dr. Kalinsky noted.
Study participants were randomly assigned to receive either standard chemotherapy plus endocrine therapy or endocrine therapy alone. Follow-up was for a median of 5 years before the current preplanned analysis.
Over a median follow-up of 5.1 years, there were 447 observed invasive disease-free survival (IDFS) events, the primary endpoint, which is 54% of the expected number at final analysis.
Across the whole cohort, adding chemotherapy to endocrine therapy was associated with a significant improvement in IDFS, with a 5-year rate of 92.4% vs 91.0% for endocrine therapy (P = .026).
Among the postmenopausal women, no such improvement was seen. The 5-year IDFS rate was 91.6% with chemotherapy plus endocrine therapy and 91.9% with endocrine therapy alone (P = .82).
Among premenopausal women, there was improvement in IDFS. The 5-year rate was 94.2% with chemotherapy plus endocrine therapy and 89.0% for endocrine therapy alone (P = .0004).
These differences were reflected in the results for overall survival. For postmenopausal women, there was a nonsignificant difference in 5-year overall survival rates (96.2% vs. 96.1%).
On the other hand, for premenopausal women, there was a significant difference in 5-year overall survival rates (98.6% vs. 97.3%; P = .032).
Stratifying patients by recurrence score, 0-13 versus 14-25, and by involvement of one versus two to three nodes did not have a major impact on the results, said Dr. Kalinsky, who also noted that future analyses will include quality of life and other outcomes.
More about endocrine therapy in RxPONDER
Dr. Osborne said that premenopausal women in RxPONDER were “nearly always” prescribed tamoxifen.
However, he observed that the current standard approach to treatment in this age group would be ovarian suppression plus either an aromatase inhibitor or tamoxifen, “both of which have been shown to be superior to tamoxifen alone in this subgroup.
“Since the adjuvant chemotherapy causes ovarian suppression in many premenopausal patients,” he said, “these patients then, in fact, received ovarian suppression plus tamoxifen,” rather than tamoxifen alone for the group that did not receive chemotherapy.
Dr. Osborne asked a question that came up again and again during the postpresentation discussion: “Is the difference in outcome in this subset due to the endocrine effects of chemotherapy? Unfortunately, we may never know the answer to this question,” he said.
Dr. Kalinsky replied that whether the difference in benefit of chemotherapy in premenopausal women “was a direct benefit, meaning that there’s something about the biology difference” between tumors in premenopausal versus postmenopausal women, “or whether this was an indirect effect, meaning impacting rates of amenorrhea... is not specifically how this study was designed.”
However, an exploratory landmark analysis at 6 months suggested that the use of ovarian suppression with endocrine therapy did not have an effect on outcomes.
Dr. Osborne said he is nevertheless “still skeptical that chemotherapy works differently in premenopausal women. Until we show that it’s not an endocrine effect ... I just can’t imagine why that group of patients, even the ones with very low Oncotype [score], would have a different response to chemotherapy.”
He added: “If I can think of a rationale ... I would believe it, but right now, I’m a little bit skeptical.”
Virginia Kaklamani, MD, of the University of Texas Health San Antonio Cancer Center, San Antonio, who is a meeting codirector, said she wanted to “second that.
“I honestly think that this is an OFS [ovarian function suppression effect] that we are seeing. We have several clinical trials that have been done looking at ovarian function suppression versus not ... showing that [it] can help as much as chemotherapy.”
Dr. Kaklamani continued: “Unfortunately, the arms to those trials were not perfect for now, and this is going to be an unanswered question until we have a large trial comparing OFS to chemotherapy.”
The study was sponsored by the National Cancer Institute, the Susan G. Komen for the Cure Research Program, the Hope Foundation for Cancer Research, the Breast Cancer Research Foundation, and Exact Sciences. Dr. Kalinsky, Dr. Osborne, and Dr. Kaklamani report financial ties to multiple pharmaceutical companies.
This article first appeared on Medscape.com.
More women with early-stage breast cancer may safely forgo chemotherapy, suggests an interim analysis of the large-scale phase 3 RxPONDER trial, presented at the San Antonio Breast Cancer Symposium 2020.
The investigators reported that adding chemotherapy to endocrine therapy did not improve outcomes for postmenopausal women with low-risk, node-positive, hormone receptor–positive (HR+), HER2-negative (HER2–) breast cancer in comparison with endocrine therapy alone.
These results are akin to those from the TAILORx trial. The results of that trial were first presented in 2018 and have changed practice for women with early-stage disease who have no lymph node involvement.
Clinicians celebrated the new results for women with lymph node–positive disease.
“RxPonder: practice changing!!!” tweeted meeting attendee Sarah Sammons, MD, Duke Cancer Center, Durham, N.C.
“Data from RxPonder are the most clinically important this year at @SABCSSanAntonio,” tweeted Hal Burstein, MD, Dana Farber Cancer Institute, Boston, who was not involved in the study.
“This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions,” asserted study lead author Kevin Kalinsky, MD, Winship Cancer Institute of Emory University, Atlanta, during a meeting press conference.
But the trial, run by the SWOG Cancer Research Network, was not without controversy.
That’s because the trial also included premenopausal women whose disease characteristics were the same and who were found to have benefited from chemotherapy.
It was not clear whether the benefit was from chemotherapy’s cytotoxicity or its endocrine effects/ovarian suppression (which limits the production of estrogen, a breast cell stimulant) in these young women. But multiple experts asserted that the effect was very likely from ovarian suppression.
“There are less toxic ways than chemo to suppress ovarian function,” tweeted Tatiana Prowell, MD, Johns Hopkins University, Baltimore, who is not a study investigator.
Some experts strongly doubted the findings in premenopausal women.
“I hate to come away with the message that all [low-risk, node-positive] premenopausal patients should get chemotherapy,” summarized C. Kent Osborne, MD, Baylor College of Medicine, Houston, who is codirector of SABCS and was not involved in the study.
RxPONDER will follow patients for 15 years, so additional data and insights will follow, observed SWOG in a press statement.
Women had limited positive nodes
RxPONDER, or SWOG S1007, involved more than 5000 women who had HR+, HER2– breast cancer with involvement of one to three lymph nodes. The patients’ recurrence score was ≤25 on a 21-tumor gene expression assay (Oncotype Dx), which is characterized as low risk.
Approximately 20% of U.S. women with nonmetastatic HR+, HER2– breast cancer present with involvement of one to three lymph nodes, Dr. Kalinsky noted.
Study participants were randomly assigned to receive either standard chemotherapy plus endocrine therapy or endocrine therapy alone. Follow-up was for a median of 5 years before the current preplanned analysis.
Over a median follow-up of 5.1 years, there were 447 observed invasive disease-free survival (IDFS) events, the primary endpoint, which is 54% of the expected number at final analysis.
Across the whole cohort, adding chemotherapy to endocrine therapy was associated with a significant improvement in IDFS, with a 5-year rate of 92.4% vs 91.0% for endocrine therapy (P = .026).
Among the postmenopausal women, no such improvement was seen. The 5-year IDFS rate was 91.6% with chemotherapy plus endocrine therapy and 91.9% with endocrine therapy alone (P = .82).
Among premenopausal women, there was improvement in IDFS. The 5-year rate was 94.2% with chemotherapy plus endocrine therapy and 89.0% for endocrine therapy alone (P = .0004).
These differences were reflected in the results for overall survival. For postmenopausal women, there was a nonsignificant difference in 5-year overall survival rates (96.2% vs. 96.1%).
On the other hand, for premenopausal women, there was a significant difference in 5-year overall survival rates (98.6% vs. 97.3%; P = .032).
Stratifying patients by recurrence score, 0-13 versus 14-25, and by involvement of one versus two to three nodes did not have a major impact on the results, said Dr. Kalinsky, who also noted that future analyses will include quality of life and other outcomes.
More about endocrine therapy in RxPONDER
Dr. Osborne said that premenopausal women in RxPONDER were “nearly always” prescribed tamoxifen.
However, he observed that the current standard approach to treatment in this age group would be ovarian suppression plus either an aromatase inhibitor or tamoxifen, “both of which have been shown to be superior to tamoxifen alone in this subgroup.
“Since the adjuvant chemotherapy causes ovarian suppression in many premenopausal patients,” he said, “these patients then, in fact, received ovarian suppression plus tamoxifen,” rather than tamoxifen alone for the group that did not receive chemotherapy.
Dr. Osborne asked a question that came up again and again during the postpresentation discussion: “Is the difference in outcome in this subset due to the endocrine effects of chemotherapy? Unfortunately, we may never know the answer to this question,” he said.
Dr. Kalinsky replied that whether the difference in benefit of chemotherapy in premenopausal women “was a direct benefit, meaning that there’s something about the biology difference” between tumors in premenopausal versus postmenopausal women, “or whether this was an indirect effect, meaning impacting rates of amenorrhea... is not specifically how this study was designed.”
However, an exploratory landmark analysis at 6 months suggested that the use of ovarian suppression with endocrine therapy did not have an effect on outcomes.
Dr. Osborne said he is nevertheless “still skeptical that chemotherapy works differently in premenopausal women. Until we show that it’s not an endocrine effect ... I just can’t imagine why that group of patients, even the ones with very low Oncotype [score], would have a different response to chemotherapy.”
He added: “If I can think of a rationale ... I would believe it, but right now, I’m a little bit skeptical.”
Virginia Kaklamani, MD, of the University of Texas Health San Antonio Cancer Center, San Antonio, who is a meeting codirector, said she wanted to “second that.
“I honestly think that this is an OFS [ovarian function suppression effect] that we are seeing. We have several clinical trials that have been done looking at ovarian function suppression versus not ... showing that [it] can help as much as chemotherapy.”
Dr. Kaklamani continued: “Unfortunately, the arms to those trials were not perfect for now, and this is going to be an unanswered question until we have a large trial comparing OFS to chemotherapy.”
The study was sponsored by the National Cancer Institute, the Susan G. Komen for the Cure Research Program, the Hope Foundation for Cancer Research, the Breast Cancer Research Foundation, and Exact Sciences. Dr. Kalinsky, Dr. Osborne, and Dr. Kaklamani report financial ties to multiple pharmaceutical companies.
This article first appeared on Medscape.com.
FROM SABCS 2020
Diabetes prevention diet may lower mortality risk in breast cancer
Women who more closely followed a diabetes risk-reduction diet both before and after a diagnosis of breast cancer had lower risks for breast cancer–specific and all-cause mortality when compared with women with less healthy diets or those who did not substantially modify what they ate following diagnosis, according to pooled data from two prospective cohort studies.
Among more than 8,000 participants in the Nurses’ Health Study and NHS II, those who most closely adhered to a dietary pattern associated with lower risk for type 2 diabetes had a 13% lower risk for breast cancer–specific mortality and a 31% lower risk for death from any cause, compared with those at the bottom of the diabetes risk-reduction diet chart, reported Tengteng Wang, PhD, of the Harvard School of Public Health, Boston, and colleagues.
“Promoting dietary changes consistent with prevention of type 2 diabetes may be very important for breast cancer survivors,” Dr. Wang said in an oral abstract presentation at the 2020 San Antonio Breast Cancer Symposium.
Poor outcomes
Type 2 diabetes has been shown to be associated with poor outcomes for women with breast cancer, prompting the investigators to see whether diet modification could play a role in improving prognosis.
They looked at self-reported dietary data from 8,320 women diagnosed with stage I-III breast cancer who were participants in NHS, with data from 1980 to 2014, and NHS II, with data from 1991 to 2015.
Every 2-4 years, participants filled out validated follow-up questionnaires, including information on diet.
The investigators calculated a diabetes risk-reduction diet (DRRD) adherence score based on nine components, including higher intakes of cereal fiber, coffee, nuts, and whole fruits, as well as a higher polyunsatured to saturated fat ratio, and lower glycemic index, plus lower intakes of trans fats, sugar-sweetened beverages and/or fruit juices, and red meat.
The investigators calculated cumulative average DRRD scores based on repeated measures of diet after breast cancer diagnosis. They obtained data on deaths from family reports or the National Death Index, and they determined causes of death from either death certificates or medical records.
At a median follow-up of 13 years, 2,146 participants had died, with 948 of the deaths attributed to breast cancer.
After adjusting for socioeconomic factors, postdiagnosis time-varying covariates, and key breast cancer clinical factors, there was a nonsignificant trend toward a lower risk for breast cancer–specific deaths in the women in the highest versus lowest quintiles of DRRD score (hazard ratio, 0.87; P = .13), but significantly lower risk for all-cause mortality risk (HR, 0.69; P < .0001).
Looking at participants who changed their diet following breast cancer diagnosis, those who went from a low DRRD score prediagnosis to a high score post diagnosis had a 20% reduction in risk for breast cancer–specific mortality and a 14% reduction in risk for all-cause mortality, the investigators found (P values for this analysis were not shown).
There were no differences in results by either tumor estrogen receptor status or stage.
Dr. Wang acknowledged that the study was limited by the population (which was predominantly composed of educated, non-Hispanic White women), errors in dietary measurement, and limited power for estrogen receptor–negative tumor analysis.
Will patients do what’s good for them?
While this study adds to the body of evidence linking diet and cancer, putting the information into action is another story, according to Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.
“We have had supportive data for the role of diet in general health outcomes, including cancer-related outcomes, for a long time. But getting the public to implement these dietary changes is a challenge, so certainly the more convincing data that we have and the more specific we can be with specific types of dietary interventions, it does make it more helpful to counsel patients,” Dr. Moore said in an interview.
She said the finding that dietary change post diagnosis can have a significant effect on lowering both all-cause and breast cancer–specific mortality is compelling evidence for a role of diet in breast cancer outcomes.
In the question-and-answer session following Dr. Wang’s presentation, Hans-Christian Kolberg, MD, from Marienhospital Bottrop at the University of Duisburg-Essen (Germany), echoed the sentiment when he commented, “you have an important result that you did not mention in the conclusion: It is not too late to change diet after breast cancer diagnosis!”
This study was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang, Dr. Moore, and Dr. Kolberg reported no relevant conflicts of interest.
SOURCE: Wang T et al. SABCS 2020, Abstract GS2-09.
Women who more closely followed a diabetes risk-reduction diet both before and after a diagnosis of breast cancer had lower risks for breast cancer–specific and all-cause mortality when compared with women with less healthy diets or those who did not substantially modify what they ate following diagnosis, according to pooled data from two prospective cohort studies.
Among more than 8,000 participants in the Nurses’ Health Study and NHS II, those who most closely adhered to a dietary pattern associated with lower risk for type 2 diabetes had a 13% lower risk for breast cancer–specific mortality and a 31% lower risk for death from any cause, compared with those at the bottom of the diabetes risk-reduction diet chart, reported Tengteng Wang, PhD, of the Harvard School of Public Health, Boston, and colleagues.
“Promoting dietary changes consistent with prevention of type 2 diabetes may be very important for breast cancer survivors,” Dr. Wang said in an oral abstract presentation at the 2020 San Antonio Breast Cancer Symposium.
Poor outcomes
Type 2 diabetes has been shown to be associated with poor outcomes for women with breast cancer, prompting the investigators to see whether diet modification could play a role in improving prognosis.
They looked at self-reported dietary data from 8,320 women diagnosed with stage I-III breast cancer who were participants in NHS, with data from 1980 to 2014, and NHS II, with data from 1991 to 2015.
Every 2-4 years, participants filled out validated follow-up questionnaires, including information on diet.
The investigators calculated a diabetes risk-reduction diet (DRRD) adherence score based on nine components, including higher intakes of cereal fiber, coffee, nuts, and whole fruits, as well as a higher polyunsatured to saturated fat ratio, and lower glycemic index, plus lower intakes of trans fats, sugar-sweetened beverages and/or fruit juices, and red meat.
The investigators calculated cumulative average DRRD scores based on repeated measures of diet after breast cancer diagnosis. They obtained data on deaths from family reports or the National Death Index, and they determined causes of death from either death certificates or medical records.
At a median follow-up of 13 years, 2,146 participants had died, with 948 of the deaths attributed to breast cancer.
After adjusting for socioeconomic factors, postdiagnosis time-varying covariates, and key breast cancer clinical factors, there was a nonsignificant trend toward a lower risk for breast cancer–specific deaths in the women in the highest versus lowest quintiles of DRRD score (hazard ratio, 0.87; P = .13), but significantly lower risk for all-cause mortality risk (HR, 0.69; P < .0001).
Looking at participants who changed their diet following breast cancer diagnosis, those who went from a low DRRD score prediagnosis to a high score post diagnosis had a 20% reduction in risk for breast cancer–specific mortality and a 14% reduction in risk for all-cause mortality, the investigators found (P values for this analysis were not shown).
There were no differences in results by either tumor estrogen receptor status or stage.
Dr. Wang acknowledged that the study was limited by the population (which was predominantly composed of educated, non-Hispanic White women), errors in dietary measurement, and limited power for estrogen receptor–negative tumor analysis.
Will patients do what’s good for them?
While this study adds to the body of evidence linking diet and cancer, putting the information into action is another story, according to Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.
“We have had supportive data for the role of diet in general health outcomes, including cancer-related outcomes, for a long time. But getting the public to implement these dietary changes is a challenge, so certainly the more convincing data that we have and the more specific we can be with specific types of dietary interventions, it does make it more helpful to counsel patients,” Dr. Moore said in an interview.
She said the finding that dietary change post diagnosis can have a significant effect on lowering both all-cause and breast cancer–specific mortality is compelling evidence for a role of diet in breast cancer outcomes.
In the question-and-answer session following Dr. Wang’s presentation, Hans-Christian Kolberg, MD, from Marienhospital Bottrop at the University of Duisburg-Essen (Germany), echoed the sentiment when he commented, “you have an important result that you did not mention in the conclusion: It is not too late to change diet after breast cancer diagnosis!”
This study was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang, Dr. Moore, and Dr. Kolberg reported no relevant conflicts of interest.
SOURCE: Wang T et al. SABCS 2020, Abstract GS2-09.
Women who more closely followed a diabetes risk-reduction diet both before and after a diagnosis of breast cancer had lower risks for breast cancer–specific and all-cause mortality when compared with women with less healthy diets or those who did not substantially modify what they ate following diagnosis, according to pooled data from two prospective cohort studies.
Among more than 8,000 participants in the Nurses’ Health Study and NHS II, those who most closely adhered to a dietary pattern associated with lower risk for type 2 diabetes had a 13% lower risk for breast cancer–specific mortality and a 31% lower risk for death from any cause, compared with those at the bottom of the diabetes risk-reduction diet chart, reported Tengteng Wang, PhD, of the Harvard School of Public Health, Boston, and colleagues.
“Promoting dietary changes consistent with prevention of type 2 diabetes may be very important for breast cancer survivors,” Dr. Wang said in an oral abstract presentation at the 2020 San Antonio Breast Cancer Symposium.
Poor outcomes
Type 2 diabetes has been shown to be associated with poor outcomes for women with breast cancer, prompting the investigators to see whether diet modification could play a role in improving prognosis.
They looked at self-reported dietary data from 8,320 women diagnosed with stage I-III breast cancer who were participants in NHS, with data from 1980 to 2014, and NHS II, with data from 1991 to 2015.
Every 2-4 years, participants filled out validated follow-up questionnaires, including information on diet.
The investigators calculated a diabetes risk-reduction diet (DRRD) adherence score based on nine components, including higher intakes of cereal fiber, coffee, nuts, and whole fruits, as well as a higher polyunsatured to saturated fat ratio, and lower glycemic index, plus lower intakes of trans fats, sugar-sweetened beverages and/or fruit juices, and red meat.
The investigators calculated cumulative average DRRD scores based on repeated measures of diet after breast cancer diagnosis. They obtained data on deaths from family reports or the National Death Index, and they determined causes of death from either death certificates or medical records.
At a median follow-up of 13 years, 2,146 participants had died, with 948 of the deaths attributed to breast cancer.
After adjusting for socioeconomic factors, postdiagnosis time-varying covariates, and key breast cancer clinical factors, there was a nonsignificant trend toward a lower risk for breast cancer–specific deaths in the women in the highest versus lowest quintiles of DRRD score (hazard ratio, 0.87; P = .13), but significantly lower risk for all-cause mortality risk (HR, 0.69; P < .0001).
Looking at participants who changed their diet following breast cancer diagnosis, those who went from a low DRRD score prediagnosis to a high score post diagnosis had a 20% reduction in risk for breast cancer–specific mortality and a 14% reduction in risk for all-cause mortality, the investigators found (P values for this analysis were not shown).
There were no differences in results by either tumor estrogen receptor status or stage.
Dr. Wang acknowledged that the study was limited by the population (which was predominantly composed of educated, non-Hispanic White women), errors in dietary measurement, and limited power for estrogen receptor–negative tumor analysis.
Will patients do what’s good for them?
While this study adds to the body of evidence linking diet and cancer, putting the information into action is another story, according to Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.
“We have had supportive data for the role of diet in general health outcomes, including cancer-related outcomes, for a long time. But getting the public to implement these dietary changes is a challenge, so certainly the more convincing data that we have and the more specific we can be with specific types of dietary interventions, it does make it more helpful to counsel patients,” Dr. Moore said in an interview.
She said the finding that dietary change post diagnosis can have a significant effect on lowering both all-cause and breast cancer–specific mortality is compelling evidence for a role of diet in breast cancer outcomes.
In the question-and-answer session following Dr. Wang’s presentation, Hans-Christian Kolberg, MD, from Marienhospital Bottrop at the University of Duisburg-Essen (Germany), echoed the sentiment when he commented, “you have an important result that you did not mention in the conclusion: It is not too late to change diet after breast cancer diagnosis!”
This study was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang, Dr. Moore, and Dr. Kolberg reported no relevant conflicts of interest.
SOURCE: Wang T et al. SABCS 2020, Abstract GS2-09.
FROM SABCS 2020
monarchE: Abemaciclib reigns on in high-risk breast cancer
The addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy continues to offer improved event-free survival in women with high-risk hormone receptor-positive (HR+), HER2-negative breast cancer, indicate updated results, which now extend to about a year and a half, from the landmark monarchE trial.
However, experts warned that longer follow-up – at least to 5 years – will be required to understand the impact of the combination treatment on survival, particularly as HR+ breast cancer is associated with a high rate of late recurrences.
The research was presented Dec. 9 at the 2020 San Antonio Breast Cancer Symposium, being held online this year because of the pandemic.
An earlier preplanned interim analysis the phase 3 trial of over 5600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.
As previously reported by Medscape Medical News, this showed that, after a median follow-up of 15.5 months, abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of invasive disease-free survival (IDFS) vs endocrine therapy alone.
At the time, the findings were hailed as practice changing and, once approved for high-risk HR+ HER2-negative early breast cancer, as the “new standard of care” by one expert.
Now, with median follow-up extended to 19.1 months, Priya Rastogi, MD, associate professor at the University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, presented new study data, including additional results on patients with a Ki-67 index ≥20%, which is indicative of fast tumor growth.
Abemaciclib plus endocrine therapy was associated with a significant 28.7% reduction in the relative risk of developing an IDFS event vs endocrine therapy alone across the whole patient population, and with a 30.9% risk reduction in those with a Ki-67 index ≥20%.
Moreover, patients taking the drug combination had a significant 31.3% reduction in the relative risk of a distant relapse-free survival (DRFS) event.
Crucially, these improvements, which were deemed clinically meaningful, were not gained at the expense of additional safety concerns, although high rates of any grade diarrhea, fatigue, and neutropenia were noted.
Rastogi said the findings underline that abemaciclib combined with standard endocrine therapy “is the first CDK4/6 inhibitor to demonstrate efficacy and tolerability for patients with HR+ HER2-negative, node-positive, high-risk early breast cancer.”
Longer follow-up is ‘reassuring’ but still ‘quite short’
George W. Sledge Jr, MD, professor of medicine at Stanford University Medical Center, Palo Alto, California, was the study discussant for the earlier interim analysis presented at ESMO 2020.
At the time, he said that the study had “very, very short follow-up,” and it was consequently unclear whether the improvements will “lead to what we really care about: improved overall survival.”
Approached to comment on the current analysis, Sledge told Medscape Medical News the data “appear quite consistent” with those presented earlier this year, “which is certainly reassuring.”
Referring to the analysis in patients with a Ki-67 index ≥20%, he added the results “show a higher absolute benefit in patients with more rapidly proliferating tumors, as might be expected for a drug affecting cell-cycle division.”
However, Sledge underlined that the median follow-up time “is still quite short for a study of ER-positive adjuvant therapy, where the majority of recurrences and deaths occur after 5 years in many studies”.
Consequently, “we still have a long way to go to understand the ultimate effects of CDK4/6 inhibition on early-stage, ER-positive breast cancer, particularly on late recurrences.”
Agreed, said C. Kent Osborne, MD, codirector of SABCS and founding director of the Duncan Cancer Center at Baylor College of Medicine, Houston, Texas.
Commenting in a press conference, he said the results are “very encouraging, especially in the subgroup of tumors with high proliferation.”
However, Osborne also urged “caution” in the interpretation of the results “given the still rather short follow-up [and] given that ER+ disease is known for its persistent recurrence rate, even past 10 years.”
He also noted “this class of inhibitors is likely cytostatic, rather than cytocidal, meaning that it blocks cell proliferation rather than killing the cells.” Questions therefore remain over whether the survival curves for combination therapy will come together with those for endocrine therapy alone once the drug is stopped.
Osborne nevertheless said that, “with these caveats in mind, this is still an extremely important trial that could be practice changing in this very high-risk patient population…if the results continue to be positive and show improved overall survival with longer follow-up.”
During the press conference, Rastogi confirmed that the study will indeed to continue out to 10 years until the final assessment of overall survival.
More study details
The 5637 women who were enrolled in monarchE were divided into two cohorts:
Cohort 1, which included patients with four or more positive nodes, or those with up to three positive nodes and a tumor size ≥5 cm or grade 3 disease
Cohort 2, which included women with up to three positive nodes and a Ki-67 index ≥20% based on a standard assay
“Cohort 2 opened one year after Cohort 1 and enrolled 517 patients,” Rastogi said.
Regardless of cohort, the patients were randomly assigned in a 1:1 fashion to abemaciclib for 2 years plus endocrine therapy for 5 to 10 years, as clinically indicated, or endocrine therapy alone.
At the primary efficacy outcome analysis, 395 IDFS events had occurred in the intention-to-treat analysis. The median follow-up was 19.1 months, and 25.5% of patients had completed the 2-year treatment period. A further 58.2% were still on treatment.
The results showed 163 IDFS events had occurred with abemaciclib plus endocrine therapy vs 232 with endocrine therapy alone, to give a 2-year IDFS rate of 92.3% vs 89.3%, at a hazard ratio of 0.713 (P = .0009).
Moving on to the subgroup analysis, Rastogi added that there were “no statistically significant interactions observed, indicating a consistent treatment benefit across all groups.”
The researchers also looked at IDFS rates in patients from both cohorts with Ki-67 index ≥20%, again finding that abemaciclib plus endocrine therapy was associated with significantly fewer events than endocrine therapy alone.
There were 82 events with the combination treatment vs 115 with endocrine therapy, at a 2-year IDFS rate of 91.6% vs 87.1% and a hazard ratio of 0.691 (P = .0111).
DRFS also significantly improved with abemaciclib plus endocrine therapy vs endocrine therapy alone, at a 2-year DRFS rate of 93.8% vs 90% or a hazard ratio of 0.687 (P = .0009).
“Safety remained consistent with the known profile of abemaciclib,” Rastogi said, “and what was observed at the second interim analysis, [with] minimal increases in any grade and grade ≥3 treatment-related adverse events.”
The most common adverse events were diarrhea, fatigue, and neutropenia, which were largely grades 1 and 2.
Notably, 2.4% of combination therapy patients experienced a venous thromboembolic event of any grade vs 0.6% of endocrine therapy patients, while 2.9% and 1.2%, respectively, had any grade interstitial lung disease.
At least one dose hold because of an adverse event was reported by 59.5% of patients on abemaciclib plus endocrine therapy, while 42.5% had at least one dose reduction because of an adverse event. In both cases, the primary reason was diarrhea.
Finally, Rastogi said that “over half of the discontinuations of abemaciclib due to adverse events occurred during the first 5 months of treatment, with the highest number…in the first month.”
Ki-67 issues
During the press conference, Virginia Kaklamani, MD, codirector of SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, asked about the practicalities of the Ki-67 index.
She said that testing is “great when it’s centrally done, but what do we expect physicians to do when some institutions do it, some don’t, and obviously it’s not really validated in most institutions around the world?”
Rastogi replied that is a “great question,” adding “this is something that is going to have to be sorted as we continue to have discussions and get more granularity of what to do when abemaciclib is administered in that patient population.”
Carlos L. Arteaga, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, Texas, added that “most of us think of 10% as a cutoff between high and low” for the Ki-67 index, rather than ≥20%.
He said that he knows it is “arbitrary” but he thinks of 20% as “extremely high” and asked whether the researchers would be able to conduct a retrospective analysis to look at Ki-67 as a gradient to determine “at what point it stops predicting.”
Rastogi replied that, at the time monarchE was developed, some of the international guidelines used a Ki-67 index ≥20% as the cutoff.
She also noted that, although Ki-67 index ≥20% was an entry criterion for cohort 2, cohort 1 patients also provided tissue after randomization, “and so we’ll be able to look at these types of questions with our translational research committee.”
This study was sponsored by Eli Lilly. Rastogi has financial ties to AstraZeneca, Genentech/Roche, and the study sponsor, Eli Lilly. Regan has ties to Lilly and multiple other pharmaceutical companies. Sledge has ties to Lilly and other companies. Osborne has ties to Lilly and other companies.
This article first appeared on Medscape.com.
The addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy continues to offer improved event-free survival in women with high-risk hormone receptor-positive (HR+), HER2-negative breast cancer, indicate updated results, which now extend to about a year and a half, from the landmark monarchE trial.
However, experts warned that longer follow-up – at least to 5 years – will be required to understand the impact of the combination treatment on survival, particularly as HR+ breast cancer is associated with a high rate of late recurrences.
The research was presented Dec. 9 at the 2020 San Antonio Breast Cancer Symposium, being held online this year because of the pandemic.
An earlier preplanned interim analysis the phase 3 trial of over 5600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.
As previously reported by Medscape Medical News, this showed that, after a median follow-up of 15.5 months, abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of invasive disease-free survival (IDFS) vs endocrine therapy alone.
At the time, the findings were hailed as practice changing and, once approved for high-risk HR+ HER2-negative early breast cancer, as the “new standard of care” by one expert.
Now, with median follow-up extended to 19.1 months, Priya Rastogi, MD, associate professor at the University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, presented new study data, including additional results on patients with a Ki-67 index ≥20%, which is indicative of fast tumor growth.
Abemaciclib plus endocrine therapy was associated with a significant 28.7% reduction in the relative risk of developing an IDFS event vs endocrine therapy alone across the whole patient population, and with a 30.9% risk reduction in those with a Ki-67 index ≥20%.
Moreover, patients taking the drug combination had a significant 31.3% reduction in the relative risk of a distant relapse-free survival (DRFS) event.
Crucially, these improvements, which were deemed clinically meaningful, were not gained at the expense of additional safety concerns, although high rates of any grade diarrhea, fatigue, and neutropenia were noted.
Rastogi said the findings underline that abemaciclib combined with standard endocrine therapy “is the first CDK4/6 inhibitor to demonstrate efficacy and tolerability for patients with HR+ HER2-negative, node-positive, high-risk early breast cancer.”
Longer follow-up is ‘reassuring’ but still ‘quite short’
George W. Sledge Jr, MD, professor of medicine at Stanford University Medical Center, Palo Alto, California, was the study discussant for the earlier interim analysis presented at ESMO 2020.
At the time, he said that the study had “very, very short follow-up,” and it was consequently unclear whether the improvements will “lead to what we really care about: improved overall survival.”
Approached to comment on the current analysis, Sledge told Medscape Medical News the data “appear quite consistent” with those presented earlier this year, “which is certainly reassuring.”
Referring to the analysis in patients with a Ki-67 index ≥20%, he added the results “show a higher absolute benefit in patients with more rapidly proliferating tumors, as might be expected for a drug affecting cell-cycle division.”
However, Sledge underlined that the median follow-up time “is still quite short for a study of ER-positive adjuvant therapy, where the majority of recurrences and deaths occur after 5 years in many studies”.
Consequently, “we still have a long way to go to understand the ultimate effects of CDK4/6 inhibition on early-stage, ER-positive breast cancer, particularly on late recurrences.”
Agreed, said C. Kent Osborne, MD, codirector of SABCS and founding director of the Duncan Cancer Center at Baylor College of Medicine, Houston, Texas.
Commenting in a press conference, he said the results are “very encouraging, especially in the subgroup of tumors with high proliferation.”
However, Osborne also urged “caution” in the interpretation of the results “given the still rather short follow-up [and] given that ER+ disease is known for its persistent recurrence rate, even past 10 years.”
He also noted “this class of inhibitors is likely cytostatic, rather than cytocidal, meaning that it blocks cell proliferation rather than killing the cells.” Questions therefore remain over whether the survival curves for combination therapy will come together with those for endocrine therapy alone once the drug is stopped.
Osborne nevertheless said that, “with these caveats in mind, this is still an extremely important trial that could be practice changing in this very high-risk patient population…if the results continue to be positive and show improved overall survival with longer follow-up.”
During the press conference, Rastogi confirmed that the study will indeed to continue out to 10 years until the final assessment of overall survival.
More study details
The 5637 women who were enrolled in monarchE were divided into two cohorts:
Cohort 1, which included patients with four or more positive nodes, or those with up to three positive nodes and a tumor size ≥5 cm or grade 3 disease
Cohort 2, which included women with up to three positive nodes and a Ki-67 index ≥20% based on a standard assay
“Cohort 2 opened one year after Cohort 1 and enrolled 517 patients,” Rastogi said.
Regardless of cohort, the patients were randomly assigned in a 1:1 fashion to abemaciclib for 2 years plus endocrine therapy for 5 to 10 years, as clinically indicated, or endocrine therapy alone.
At the primary efficacy outcome analysis, 395 IDFS events had occurred in the intention-to-treat analysis. The median follow-up was 19.1 months, and 25.5% of patients had completed the 2-year treatment period. A further 58.2% were still on treatment.
The results showed 163 IDFS events had occurred with abemaciclib plus endocrine therapy vs 232 with endocrine therapy alone, to give a 2-year IDFS rate of 92.3% vs 89.3%, at a hazard ratio of 0.713 (P = .0009).
Moving on to the subgroup analysis, Rastogi added that there were “no statistically significant interactions observed, indicating a consistent treatment benefit across all groups.”
The researchers also looked at IDFS rates in patients from both cohorts with Ki-67 index ≥20%, again finding that abemaciclib plus endocrine therapy was associated with significantly fewer events than endocrine therapy alone.
There were 82 events with the combination treatment vs 115 with endocrine therapy, at a 2-year IDFS rate of 91.6% vs 87.1% and a hazard ratio of 0.691 (P = .0111).
DRFS also significantly improved with abemaciclib plus endocrine therapy vs endocrine therapy alone, at a 2-year DRFS rate of 93.8% vs 90% or a hazard ratio of 0.687 (P = .0009).
“Safety remained consistent with the known profile of abemaciclib,” Rastogi said, “and what was observed at the second interim analysis, [with] minimal increases in any grade and grade ≥3 treatment-related adverse events.”
The most common adverse events were diarrhea, fatigue, and neutropenia, which were largely grades 1 and 2.
Notably, 2.4% of combination therapy patients experienced a venous thromboembolic event of any grade vs 0.6% of endocrine therapy patients, while 2.9% and 1.2%, respectively, had any grade interstitial lung disease.
At least one dose hold because of an adverse event was reported by 59.5% of patients on abemaciclib plus endocrine therapy, while 42.5% had at least one dose reduction because of an adverse event. In both cases, the primary reason was diarrhea.
Finally, Rastogi said that “over half of the discontinuations of abemaciclib due to adverse events occurred during the first 5 months of treatment, with the highest number…in the first month.”
Ki-67 issues
During the press conference, Virginia Kaklamani, MD, codirector of SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, asked about the practicalities of the Ki-67 index.
She said that testing is “great when it’s centrally done, but what do we expect physicians to do when some institutions do it, some don’t, and obviously it’s not really validated in most institutions around the world?”
Rastogi replied that is a “great question,” adding “this is something that is going to have to be sorted as we continue to have discussions and get more granularity of what to do when abemaciclib is administered in that patient population.”
Carlos L. Arteaga, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, Texas, added that “most of us think of 10% as a cutoff between high and low” for the Ki-67 index, rather than ≥20%.
He said that he knows it is “arbitrary” but he thinks of 20% as “extremely high” and asked whether the researchers would be able to conduct a retrospective analysis to look at Ki-67 as a gradient to determine “at what point it stops predicting.”
Rastogi replied that, at the time monarchE was developed, some of the international guidelines used a Ki-67 index ≥20% as the cutoff.
She also noted that, although Ki-67 index ≥20% was an entry criterion for cohort 2, cohort 1 patients also provided tissue after randomization, “and so we’ll be able to look at these types of questions with our translational research committee.”
This study was sponsored by Eli Lilly. Rastogi has financial ties to AstraZeneca, Genentech/Roche, and the study sponsor, Eli Lilly. Regan has ties to Lilly and multiple other pharmaceutical companies. Sledge has ties to Lilly and other companies. Osborne has ties to Lilly and other companies.
This article first appeared on Medscape.com.
The addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy continues to offer improved event-free survival in women with high-risk hormone receptor-positive (HR+), HER2-negative breast cancer, indicate updated results, which now extend to about a year and a half, from the landmark monarchE trial.
However, experts warned that longer follow-up – at least to 5 years – will be required to understand the impact of the combination treatment on survival, particularly as HR+ breast cancer is associated with a high rate of late recurrences.
The research was presented Dec. 9 at the 2020 San Antonio Breast Cancer Symposium, being held online this year because of the pandemic.
An earlier preplanned interim analysis the phase 3 trial of over 5600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.
As previously reported by Medscape Medical News, this showed that, after a median follow-up of 15.5 months, abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of invasive disease-free survival (IDFS) vs endocrine therapy alone.
At the time, the findings were hailed as practice changing and, once approved for high-risk HR+ HER2-negative early breast cancer, as the “new standard of care” by one expert.
Now, with median follow-up extended to 19.1 months, Priya Rastogi, MD, associate professor at the University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, presented new study data, including additional results on patients with a Ki-67 index ≥20%, which is indicative of fast tumor growth.
Abemaciclib plus endocrine therapy was associated with a significant 28.7% reduction in the relative risk of developing an IDFS event vs endocrine therapy alone across the whole patient population, and with a 30.9% risk reduction in those with a Ki-67 index ≥20%.
Moreover, patients taking the drug combination had a significant 31.3% reduction in the relative risk of a distant relapse-free survival (DRFS) event.
Crucially, these improvements, which were deemed clinically meaningful, were not gained at the expense of additional safety concerns, although high rates of any grade diarrhea, fatigue, and neutropenia were noted.
Rastogi said the findings underline that abemaciclib combined with standard endocrine therapy “is the first CDK4/6 inhibitor to demonstrate efficacy and tolerability for patients with HR+ HER2-negative, node-positive, high-risk early breast cancer.”
Longer follow-up is ‘reassuring’ but still ‘quite short’
George W. Sledge Jr, MD, professor of medicine at Stanford University Medical Center, Palo Alto, California, was the study discussant for the earlier interim analysis presented at ESMO 2020.
At the time, he said that the study had “very, very short follow-up,” and it was consequently unclear whether the improvements will “lead to what we really care about: improved overall survival.”
Approached to comment on the current analysis, Sledge told Medscape Medical News the data “appear quite consistent” with those presented earlier this year, “which is certainly reassuring.”
Referring to the analysis in patients with a Ki-67 index ≥20%, he added the results “show a higher absolute benefit in patients with more rapidly proliferating tumors, as might be expected for a drug affecting cell-cycle division.”
However, Sledge underlined that the median follow-up time “is still quite short for a study of ER-positive adjuvant therapy, where the majority of recurrences and deaths occur after 5 years in many studies”.
Consequently, “we still have a long way to go to understand the ultimate effects of CDK4/6 inhibition on early-stage, ER-positive breast cancer, particularly on late recurrences.”
Agreed, said C. Kent Osborne, MD, codirector of SABCS and founding director of the Duncan Cancer Center at Baylor College of Medicine, Houston, Texas.
Commenting in a press conference, he said the results are “very encouraging, especially in the subgroup of tumors with high proliferation.”
However, Osborne also urged “caution” in the interpretation of the results “given the still rather short follow-up [and] given that ER+ disease is known for its persistent recurrence rate, even past 10 years.”
He also noted “this class of inhibitors is likely cytostatic, rather than cytocidal, meaning that it blocks cell proliferation rather than killing the cells.” Questions therefore remain over whether the survival curves for combination therapy will come together with those for endocrine therapy alone once the drug is stopped.
Osborne nevertheless said that, “with these caveats in mind, this is still an extremely important trial that could be practice changing in this very high-risk patient population…if the results continue to be positive and show improved overall survival with longer follow-up.”
During the press conference, Rastogi confirmed that the study will indeed to continue out to 10 years until the final assessment of overall survival.
More study details
The 5637 women who were enrolled in monarchE were divided into two cohorts:
Cohort 1, which included patients with four or more positive nodes, or those with up to three positive nodes and a tumor size ≥5 cm or grade 3 disease
Cohort 2, which included women with up to three positive nodes and a Ki-67 index ≥20% based on a standard assay
“Cohort 2 opened one year after Cohort 1 and enrolled 517 patients,” Rastogi said.
Regardless of cohort, the patients were randomly assigned in a 1:1 fashion to abemaciclib for 2 years plus endocrine therapy for 5 to 10 years, as clinically indicated, or endocrine therapy alone.
At the primary efficacy outcome analysis, 395 IDFS events had occurred in the intention-to-treat analysis. The median follow-up was 19.1 months, and 25.5% of patients had completed the 2-year treatment period. A further 58.2% were still on treatment.
The results showed 163 IDFS events had occurred with abemaciclib plus endocrine therapy vs 232 with endocrine therapy alone, to give a 2-year IDFS rate of 92.3% vs 89.3%, at a hazard ratio of 0.713 (P = .0009).
Moving on to the subgroup analysis, Rastogi added that there were “no statistically significant interactions observed, indicating a consistent treatment benefit across all groups.”
The researchers also looked at IDFS rates in patients from both cohorts with Ki-67 index ≥20%, again finding that abemaciclib plus endocrine therapy was associated with significantly fewer events than endocrine therapy alone.
There were 82 events with the combination treatment vs 115 with endocrine therapy, at a 2-year IDFS rate of 91.6% vs 87.1% and a hazard ratio of 0.691 (P = .0111).
DRFS also significantly improved with abemaciclib plus endocrine therapy vs endocrine therapy alone, at a 2-year DRFS rate of 93.8% vs 90% or a hazard ratio of 0.687 (P = .0009).
“Safety remained consistent with the known profile of abemaciclib,” Rastogi said, “and what was observed at the second interim analysis, [with] minimal increases in any grade and grade ≥3 treatment-related adverse events.”
The most common adverse events were diarrhea, fatigue, and neutropenia, which were largely grades 1 and 2.
Notably, 2.4% of combination therapy patients experienced a venous thromboembolic event of any grade vs 0.6% of endocrine therapy patients, while 2.9% and 1.2%, respectively, had any grade interstitial lung disease.
At least one dose hold because of an adverse event was reported by 59.5% of patients on abemaciclib plus endocrine therapy, while 42.5% had at least one dose reduction because of an adverse event. In both cases, the primary reason was diarrhea.
Finally, Rastogi said that “over half of the discontinuations of abemaciclib due to adverse events occurred during the first 5 months of treatment, with the highest number…in the first month.”
Ki-67 issues
During the press conference, Virginia Kaklamani, MD, codirector of SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, asked about the practicalities of the Ki-67 index.
She said that testing is “great when it’s centrally done, but what do we expect physicians to do when some institutions do it, some don’t, and obviously it’s not really validated in most institutions around the world?”
Rastogi replied that is a “great question,” adding “this is something that is going to have to be sorted as we continue to have discussions and get more granularity of what to do when abemaciclib is administered in that patient population.”
Carlos L. Arteaga, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, Texas, added that “most of us think of 10% as a cutoff between high and low” for the Ki-67 index, rather than ≥20%.
He said that he knows it is “arbitrary” but he thinks of 20% as “extremely high” and asked whether the researchers would be able to conduct a retrospective analysis to look at Ki-67 as a gradient to determine “at what point it stops predicting.”
Rastogi replied that, at the time monarchE was developed, some of the international guidelines used a Ki-67 index ≥20% as the cutoff.
She also noted that, although Ki-67 index ≥20% was an entry criterion for cohort 2, cohort 1 patients also provided tissue after randomization, “and so we’ll be able to look at these types of questions with our translational research committee.”
This study was sponsored by Eli Lilly. Rastogi has financial ties to AstraZeneca, Genentech/Roche, and the study sponsor, Eli Lilly. Regan has ties to Lilly and multiple other pharmaceutical companies. Sledge has ties to Lilly and other companies. Osborne has ties to Lilly and other companies.
This article first appeared on Medscape.com.
FROM SABCS 2020
PENELOPE-B: Palbociclib disappoints in HR+, HER2– breast cancer
The CDK4/6 inhibitor palbociclib provides no significant benefit in patients with hormone receptor–positive (HR+), HER2-negative primary breast cancer, according to first results from the PENELOPE-B trial.
In this phase 3 trial, adding palbociclib to standard endocrine therapy did not improve invasive disease-free survival (iDFS) in patients who were at high risk of relapse following neoadjuvant chemotherapy (NACT).
There was no significant difference in iDFS rates with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or even 4 years (73% vs. 72.4%), with a stratified hazard ratio of 0.93 (P = .525).
“This, unfortunately, was a negative trial,” said Ruth M. O’Regan, MD, of the University of Wisconsin–Madison, who independently commented after the trial’s virtual presentation at the 2020 San Antonio Breast Cancer Symposium.
Discussing the iDFS curves for palbociclib and placebo over time, Dr. O’Regan observed that there was a slight benefit for palbociclib in the range of 4.3%, compared with placebo at 2 years and 3.5% at 3 years. The benefit was small but “still meaningful,” she added. However, “at 4 years, you can see the curves have completely come together.”
“This begs the question of whether this trial was just treating patients with occult metastatic disease because I think these curves kind of mirror what we might see in the first-line metastatic setting,” Dr. O’Regan suggested.
Study details
The PENELOPE-B trial was designed to see if palbociclib could improve iDFS in women with HR+, HER2-negative primary breast cancer who were at high risk of relapse following NACT.
The clinical-pathologic stage plus estrogen receptor and grade (CPS-EG) staging system was used to identify patients at high risk for relapse. A CPS-EG score of 3 or higher or 2 or higher with nodal involvement was used as an entry criterion. This has been associated with a 3-year disease-free survival rate of 77%, noted Sibylle Loibl, MD, PhD, head of the German Breast Group in Neu-Isenburg, who presented PENELOPE-B data at the meeting.
The trial enrolled 1,250 women who did not have a pathological complete response after NACT. After surgery, with or without radiotherapy, patients were randomized to receive 13 cycles of either palbociclib or placebo (125 mg once daily; 21 days on and 7 days off treatment). All patients received concomitant endocrine therapy according to local standards.
“Although the compliance was lower in the palbociclib arm than the placebo arm, it was still satisfactory, and the relative dose intensity was over 80%,” Dr. Loibl noted.
The primary endpoint was iDFS rate. As noted previously, there were no significant between-arm differences in 2-, 3-, or 4-year iDFS rates.
Likewise, there were no significant differences between palbociclib and placebo in terms of the secondary endpoints, which included the type of iDFS event (distant recurrences, invasive locoregional recurrences, contralateral breast cancer, second primary invasive nonbreast cancer, and death without previous event).
Subgroup iDFS analyses showed no differences between the study arms. “No group could be identified with a higher benefit from palbociclib,” Dr. Loibl reported.
An interim overall survival (OS) analysis showed no significant differences between palbociclib and placebo. The 2-year OS rate was 96.3% with palbociclib and 94.5% with placebo. The 3-year OS rates were 93.6% and 90.5%, respectively. The 4-year OS rates were 90.4% and 87.3%, respectively.
“Today, the results of the PENELOPE-B study do not support the addition of 1 year of palbociclib to endocrine therapy. Long-term follow up from all neoadjuvant CDK4/6 inhibitor studies should continue and must be awaited,” Dr. Loibl concluded.
Findings in context
PENELOPE-B is the second phase 3 trial to show no benefit for palbociclib in the treatment of early high-risk breast cancer. The first was the PALLAS trial, which was reported only a few months ago at the European Society for Medical Oncology Virtual Congress 2020.
In PALLAS, palbociclib plus endocrine therapy was compared with endocrine therapy alone in the treatment of women with HR+, HER2-negative early breast cancer, but there was no additional benefit seen.
The results of both PENELOPE-B and PALLAS contrast those recently seen with another CDK4/6 inhibitor, abemaciclib, in HR+/HER2-negative early breast cancer.
Results of the phase 3 monarchE trial showed that, when abemaciclib was added to endocrine treatment, there was a significant (P = .0096) 25% relative risk reduction (HR, 0.75; 95% confidence interval, 0.60-0.93) in iDFS, compared with endocrine therapy alone. These results were also presented at the ESMO Virtual Congress 2020 and published in the Journal of Clinical Oncology.
While it’s not clear why one CDK4/6 inhibitor may be of benefit in HR+/HER2-negative early breast cancer while the other is not, “PENELOPE-B is clearly quite a different trial to the other two adjuvant CDK inhibitor trials,” Dr. O’Regan observed.
For one thing, PENELOPE-B participants were only eligible for the trial if they did not have a pathological complete response after NACT. In addition, PENELOPE-B is a smaller trial, enrolling well under a third of the number of patients who participated in the PALLAS and monarchE trials. Furthermore, the CPS-EG score, rather than anatomic staging, was used to determine eligibility.
“Abemaciclib could be a more effective CDK inhibitor; that’s most certainly a possibility,” Dr. O’Regan suggested. “However, it’s not supported by the metastatic first-line trials, which have remarkably similar hazard ratios and favor CDK inhibitors.”
Perhaps the shorter duration of palbociclib treatment in the PENELOPE-B trial (12 months vs. 24 months) had an effect.
“Clearly, we need to await the results of NATALEE that uses 3 years of ribociclib,” Dr. O’Regan said. It also remains to be seen if the results of the monarchE trial hold up with longer follow-up.
The PENELOPE-B trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study and relationships with other companies outside the submitted work. She also disclosed intellectual property rights and being a pending patent holder (EP14153692.0) for a method to predict response to anti-HER2–containing therapy and/or chemotherapy in patients with breast cancer, and she disclosed a relationship with Medscape, which is owned by the same company as MDedge. Dr. O’Regan disclosed relationships with Novartis, Eli Lilly, Genentech, PUMA, Macrogenics, Immunomedics, Biotheranostics, and Eisai.
SOURCE: Loibl S et al. SABCS 2020, Abstract GS1-02.
The CDK4/6 inhibitor palbociclib provides no significant benefit in patients with hormone receptor–positive (HR+), HER2-negative primary breast cancer, according to first results from the PENELOPE-B trial.
In this phase 3 trial, adding palbociclib to standard endocrine therapy did not improve invasive disease-free survival (iDFS) in patients who were at high risk of relapse following neoadjuvant chemotherapy (NACT).
There was no significant difference in iDFS rates with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or even 4 years (73% vs. 72.4%), with a stratified hazard ratio of 0.93 (P = .525).
“This, unfortunately, was a negative trial,” said Ruth M. O’Regan, MD, of the University of Wisconsin–Madison, who independently commented after the trial’s virtual presentation at the 2020 San Antonio Breast Cancer Symposium.
Discussing the iDFS curves for palbociclib and placebo over time, Dr. O’Regan observed that there was a slight benefit for palbociclib in the range of 4.3%, compared with placebo at 2 years and 3.5% at 3 years. The benefit was small but “still meaningful,” she added. However, “at 4 years, you can see the curves have completely come together.”
“This begs the question of whether this trial was just treating patients with occult metastatic disease because I think these curves kind of mirror what we might see in the first-line metastatic setting,” Dr. O’Regan suggested.
Study details
The PENELOPE-B trial was designed to see if palbociclib could improve iDFS in women with HR+, HER2-negative primary breast cancer who were at high risk of relapse following NACT.
The clinical-pathologic stage plus estrogen receptor and grade (CPS-EG) staging system was used to identify patients at high risk for relapse. A CPS-EG score of 3 or higher or 2 or higher with nodal involvement was used as an entry criterion. This has been associated with a 3-year disease-free survival rate of 77%, noted Sibylle Loibl, MD, PhD, head of the German Breast Group in Neu-Isenburg, who presented PENELOPE-B data at the meeting.
The trial enrolled 1,250 women who did not have a pathological complete response after NACT. After surgery, with or without radiotherapy, patients were randomized to receive 13 cycles of either palbociclib or placebo (125 mg once daily; 21 days on and 7 days off treatment). All patients received concomitant endocrine therapy according to local standards.
“Although the compliance was lower in the palbociclib arm than the placebo arm, it was still satisfactory, and the relative dose intensity was over 80%,” Dr. Loibl noted.
The primary endpoint was iDFS rate. As noted previously, there were no significant between-arm differences in 2-, 3-, or 4-year iDFS rates.
Likewise, there were no significant differences between palbociclib and placebo in terms of the secondary endpoints, which included the type of iDFS event (distant recurrences, invasive locoregional recurrences, contralateral breast cancer, second primary invasive nonbreast cancer, and death without previous event).
Subgroup iDFS analyses showed no differences between the study arms. “No group could be identified with a higher benefit from palbociclib,” Dr. Loibl reported.
An interim overall survival (OS) analysis showed no significant differences between palbociclib and placebo. The 2-year OS rate was 96.3% with palbociclib and 94.5% with placebo. The 3-year OS rates were 93.6% and 90.5%, respectively. The 4-year OS rates were 90.4% and 87.3%, respectively.
“Today, the results of the PENELOPE-B study do not support the addition of 1 year of palbociclib to endocrine therapy. Long-term follow up from all neoadjuvant CDK4/6 inhibitor studies should continue and must be awaited,” Dr. Loibl concluded.
Findings in context
PENELOPE-B is the second phase 3 trial to show no benefit for palbociclib in the treatment of early high-risk breast cancer. The first was the PALLAS trial, which was reported only a few months ago at the European Society for Medical Oncology Virtual Congress 2020.
In PALLAS, palbociclib plus endocrine therapy was compared with endocrine therapy alone in the treatment of women with HR+, HER2-negative early breast cancer, but there was no additional benefit seen.
The results of both PENELOPE-B and PALLAS contrast those recently seen with another CDK4/6 inhibitor, abemaciclib, in HR+/HER2-negative early breast cancer.
Results of the phase 3 monarchE trial showed that, when abemaciclib was added to endocrine treatment, there was a significant (P = .0096) 25% relative risk reduction (HR, 0.75; 95% confidence interval, 0.60-0.93) in iDFS, compared with endocrine therapy alone. These results were also presented at the ESMO Virtual Congress 2020 and published in the Journal of Clinical Oncology.
While it’s not clear why one CDK4/6 inhibitor may be of benefit in HR+/HER2-negative early breast cancer while the other is not, “PENELOPE-B is clearly quite a different trial to the other two adjuvant CDK inhibitor trials,” Dr. O’Regan observed.
For one thing, PENELOPE-B participants were only eligible for the trial if they did not have a pathological complete response after NACT. In addition, PENELOPE-B is a smaller trial, enrolling well under a third of the number of patients who participated in the PALLAS and monarchE trials. Furthermore, the CPS-EG score, rather than anatomic staging, was used to determine eligibility.
“Abemaciclib could be a more effective CDK inhibitor; that’s most certainly a possibility,” Dr. O’Regan suggested. “However, it’s not supported by the metastatic first-line trials, which have remarkably similar hazard ratios and favor CDK inhibitors.”
Perhaps the shorter duration of palbociclib treatment in the PENELOPE-B trial (12 months vs. 24 months) had an effect.
“Clearly, we need to await the results of NATALEE that uses 3 years of ribociclib,” Dr. O’Regan said. It also remains to be seen if the results of the monarchE trial hold up with longer follow-up.
The PENELOPE-B trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study and relationships with other companies outside the submitted work. She also disclosed intellectual property rights and being a pending patent holder (EP14153692.0) for a method to predict response to anti-HER2–containing therapy and/or chemotherapy in patients with breast cancer, and she disclosed a relationship with Medscape, which is owned by the same company as MDedge. Dr. O’Regan disclosed relationships with Novartis, Eli Lilly, Genentech, PUMA, Macrogenics, Immunomedics, Biotheranostics, and Eisai.
SOURCE: Loibl S et al. SABCS 2020, Abstract GS1-02.
The CDK4/6 inhibitor palbociclib provides no significant benefit in patients with hormone receptor–positive (HR+), HER2-negative primary breast cancer, according to first results from the PENELOPE-B trial.
In this phase 3 trial, adding palbociclib to standard endocrine therapy did not improve invasive disease-free survival (iDFS) in patients who were at high risk of relapse following neoadjuvant chemotherapy (NACT).
There was no significant difference in iDFS rates with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or even 4 years (73% vs. 72.4%), with a stratified hazard ratio of 0.93 (P = .525).
“This, unfortunately, was a negative trial,” said Ruth M. O’Regan, MD, of the University of Wisconsin–Madison, who independently commented after the trial’s virtual presentation at the 2020 San Antonio Breast Cancer Symposium.
Discussing the iDFS curves for palbociclib and placebo over time, Dr. O’Regan observed that there was a slight benefit for palbociclib in the range of 4.3%, compared with placebo at 2 years and 3.5% at 3 years. The benefit was small but “still meaningful,” she added. However, “at 4 years, you can see the curves have completely come together.”
“This begs the question of whether this trial was just treating patients with occult metastatic disease because I think these curves kind of mirror what we might see in the first-line metastatic setting,” Dr. O’Regan suggested.
Study details
The PENELOPE-B trial was designed to see if palbociclib could improve iDFS in women with HR+, HER2-negative primary breast cancer who were at high risk of relapse following NACT.
The clinical-pathologic stage plus estrogen receptor and grade (CPS-EG) staging system was used to identify patients at high risk for relapse. A CPS-EG score of 3 or higher or 2 or higher with nodal involvement was used as an entry criterion. This has been associated with a 3-year disease-free survival rate of 77%, noted Sibylle Loibl, MD, PhD, head of the German Breast Group in Neu-Isenburg, who presented PENELOPE-B data at the meeting.
The trial enrolled 1,250 women who did not have a pathological complete response after NACT. After surgery, with or without radiotherapy, patients were randomized to receive 13 cycles of either palbociclib or placebo (125 mg once daily; 21 days on and 7 days off treatment). All patients received concomitant endocrine therapy according to local standards.
“Although the compliance was lower in the palbociclib arm than the placebo arm, it was still satisfactory, and the relative dose intensity was over 80%,” Dr. Loibl noted.
The primary endpoint was iDFS rate. As noted previously, there were no significant between-arm differences in 2-, 3-, or 4-year iDFS rates.
Likewise, there were no significant differences between palbociclib and placebo in terms of the secondary endpoints, which included the type of iDFS event (distant recurrences, invasive locoregional recurrences, contralateral breast cancer, second primary invasive nonbreast cancer, and death without previous event).
Subgroup iDFS analyses showed no differences between the study arms. “No group could be identified with a higher benefit from palbociclib,” Dr. Loibl reported.
An interim overall survival (OS) analysis showed no significant differences between palbociclib and placebo. The 2-year OS rate was 96.3% with palbociclib and 94.5% with placebo. The 3-year OS rates were 93.6% and 90.5%, respectively. The 4-year OS rates were 90.4% and 87.3%, respectively.
“Today, the results of the PENELOPE-B study do not support the addition of 1 year of palbociclib to endocrine therapy. Long-term follow up from all neoadjuvant CDK4/6 inhibitor studies should continue and must be awaited,” Dr. Loibl concluded.
Findings in context
PENELOPE-B is the second phase 3 trial to show no benefit for palbociclib in the treatment of early high-risk breast cancer. The first was the PALLAS trial, which was reported only a few months ago at the European Society for Medical Oncology Virtual Congress 2020.
In PALLAS, palbociclib plus endocrine therapy was compared with endocrine therapy alone in the treatment of women with HR+, HER2-negative early breast cancer, but there was no additional benefit seen.
The results of both PENELOPE-B and PALLAS contrast those recently seen with another CDK4/6 inhibitor, abemaciclib, in HR+/HER2-negative early breast cancer.
Results of the phase 3 monarchE trial showed that, when abemaciclib was added to endocrine treatment, there was a significant (P = .0096) 25% relative risk reduction (HR, 0.75; 95% confidence interval, 0.60-0.93) in iDFS, compared with endocrine therapy alone. These results were also presented at the ESMO Virtual Congress 2020 and published in the Journal of Clinical Oncology.
While it’s not clear why one CDK4/6 inhibitor may be of benefit in HR+/HER2-negative early breast cancer while the other is not, “PENELOPE-B is clearly quite a different trial to the other two adjuvant CDK inhibitor trials,” Dr. O’Regan observed.
For one thing, PENELOPE-B participants were only eligible for the trial if they did not have a pathological complete response after NACT. In addition, PENELOPE-B is a smaller trial, enrolling well under a third of the number of patients who participated in the PALLAS and monarchE trials. Furthermore, the CPS-EG score, rather than anatomic staging, was used to determine eligibility.
“Abemaciclib could be a more effective CDK inhibitor; that’s most certainly a possibility,” Dr. O’Regan suggested. “However, it’s not supported by the metastatic first-line trials, which have remarkably similar hazard ratios and favor CDK inhibitors.”
Perhaps the shorter duration of palbociclib treatment in the PENELOPE-B trial (12 months vs. 24 months) had an effect.
“Clearly, we need to await the results of NATALEE that uses 3 years of ribociclib,” Dr. O’Regan said. It also remains to be seen if the results of the monarchE trial hold up with longer follow-up.
The PENELOPE-B trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study and relationships with other companies outside the submitted work. She also disclosed intellectual property rights and being a pending patent holder (EP14153692.0) for a method to predict response to anti-HER2–containing therapy and/or chemotherapy in patients with breast cancer, and she disclosed a relationship with Medscape, which is owned by the same company as MDedge. Dr. O’Regan disclosed relationships with Novartis, Eli Lilly, Genentech, PUMA, Macrogenics, Immunomedics, Biotheranostics, and Eisai.
SOURCE: Loibl S et al. SABCS 2020, Abstract GS1-02.
FROM SABCS 2020
Breast surgery may be a gateway to addictive medication use
After their surgery, 13.1% of opioid-naive patients become new persistent opioid users, and 6.6% of sedative-hypnotic–naive patients become new persistent users of sedative-hypnotics. Risk factors for persistent substance use included younger age, a breast cancer diagnosis, and chemotherapy.
“As the opioid epidemic in the United States continues, the rate of opioid dependence in the cancer population continues to increase as well,” study investigator Jacob Cogan, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York, said during a press conference.
“The perioperative period is one of high risk for cancer patients, with up to 10% becoming new persistent opioid users after cancer-related surgery. The rates surrounding mastectomy and reconstruction, however, are unknown. Another class of controlled substances worth our attention are the sedative-hypnotics. Despite the high rates of psychiatric disorders in the cancer population, there is little research into the rates of persistent sedative-hypnotic use in these patients.”
With this in mind, Dr. Cogan and colleagues analyzed MarketScan health care claims data for patients who underwent mastectomy and reconstruction (whether therapeutic or prophylactic) between 2008 and 2017.
The researchers then identified prescription claims for opioids and sedative-hypnotics during three periods:
- Preoperative period – 365 days to 31 days before surgery.
- Perioperative period – 31 days before to 90 days after surgery.
- Postoperative period – 90 days to 365 days after surgery.
‘Striking’ results
Analyses were based on 25,270 women who were not prior users of opioids and 27,651 women who were not prior users of sedative-hypnotics.
Women were considered new persistent substance users if they had no use in the preoperative period but filled at least one prescription in the perioperative period and at least two in the postoperative period.
Overall, 13.1% of opioid-naive patients became persistent opioid users, and 6.6% of sedative-hypnotic-naive patients became persistent sedative-hypnotic users after their mastectomy and reconstruction.
Proportions of substance use were even higher, 17.5% for opioids and 17.0% for sedative-hypnotics, after excluding women who did not receive or fill a perioperative prescription.
In multivariate analysis, patients were significantly more likely to become new persistent opioid users if they had Medicaid insurance (odds ratio, 2.31), had a breast cancer diagnosis vs a prophylactic indication (OR, 1.44), received chemotherapy (OR, 1.33), and were 50-64 years of age (OR, 1.29) or 49 years or younger (OR, 1.27), compared with 65 years or older.
Similarly, patients were significantly more likely to become new persistent sedative-hypnotic users if they received chemotherapy (OR, 2.24), had Medicaid insurance (OR, 1.85), had a breast cancer diagnosis (OR, 1.79), and were 50 to 64 years (OR, 1.65) or 49 years or younger (OR, 1.79).
Finally, patients’ likelihood of new persistent use increased with their number of risk factors. For persistent opioid use, the odds ratio rose from 2.27 in patients with two risk factors to 6.34 in those with five risk factors. For persistent sedative-hypnotic use, the odds ratio rose from 2.55 to 7.71, respectively.
The observed incidences of new persistent substance use in this patient population are “striking,” according to Dr. Cogan. Although the identified risk factors can help providers spot patients who should be monitored more closely, a proactive, systematic approach to postoperative follow-up for all patients is likely needed.
“When you are seeing patients in follow-up, this is something that you might want to explicitly ask about, for example, and not just assume that the postoperative opioids were taken and then disposed of,” Dr. Cogan recommended. “Ask them, ‘Are you still taking opioids, are you still taking your Ambien or whatever medication you were prescribed?’ That’s something to diligently follow up on and make sure the drug is disposed of, or if it somebody is still taking it, refer them for the appropriate services.”
In addition, patients should be encouraged to use over-the-counter medications as much as possible, he advised.
Prescribing: It’s complicated
“I wonder if perhaps we should not be giving opioids at all to certain patients. For example, a mastectomy and implant reconstruction, oftentimes, surprisingly, that’s not a terribly painful procedure. But a TRAM [transverse rectus abdominis] flap or abdominal flap, that really is,” commented press conference comoderator C. Kent Osborne, MD, of Baylor College of Medicine in Houston.
“I’ve been surprised that a lot of my patients get the prescription, but they don’t even use the pills, and I wonder if the prescription is given just so that we’re not bothered at nighttime by somebody calling with pain,” Dr. Osbourne added.
Prescribing opioids for postoperative pain is complicated, Dr. Cogan said, noting that the study did not assess the specific type of reconstruction patients had.
“You don’t want people in pain. Even if they need just one or two pills, it’s still reasonable for them to have it, and we certainly don’t want to imply from our study that people shouldn’t be getting these prescriptions if they need them,” Dr. Cogan elaborated. “But once patients have them, don’t just leave them there in their home because other studies have shown that that’s when people really get addicted to these medications, when they use them later on for other reasons, or they keep using them just because they have them around.”
The risk for persistent use of controlled substances “is something that all physicians need to be aware of for their patients. This is something that we are missing,” maintained press conference comoderator Virginia Kaklamani, MD, DSc, of UT Health San Antonio.
“It’s easy to just give a prescription instead of arguing with a patient about why you are not going to give them a prescription,” Dr. Kaklamani said. “And ultimately ... pain is subjective. If a patient tells you they are in pain, you are, quote-endquote, a bad physician if you tell them they should not be in pain.”
“We need to focus on other ways to deal with the pain, like physical therapy, sending patients to physical medicine and rehab physicians who are trained to help with symptoms from the surgery, with range of motion and all that; that can help with pain,” she recommended. “It’s much harder to do that, right, than to send a prescription in for a narcotic? But that easy answer is always the worst answer.”
This study was funded by the Breast Cancer Research Foundation and the National Institutes of Health. Dr. Cogan declared no conflicts of interest. Dr. Osborne disclosed relationships with Wolters Kluwer, Lilly, Tolmar, and GeneTex. Dr. Kaklamani disclosed relationships with Amgen, AstraZeneca, Athenex, Celgene, Celldex, Daiichi, Eisai, Genentech, Genomic Health, Immunomedics, Novartis, Pfizer, Puma, and Seattle Genetics.
SOURCE: Cogan JC et al. SABCS 2020, Abstract GS3-08.
After their surgery, 13.1% of opioid-naive patients become new persistent opioid users, and 6.6% of sedative-hypnotic–naive patients become new persistent users of sedative-hypnotics. Risk factors for persistent substance use included younger age, a breast cancer diagnosis, and chemotherapy.
“As the opioid epidemic in the United States continues, the rate of opioid dependence in the cancer population continues to increase as well,” study investigator Jacob Cogan, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York, said during a press conference.
“The perioperative period is one of high risk for cancer patients, with up to 10% becoming new persistent opioid users after cancer-related surgery. The rates surrounding mastectomy and reconstruction, however, are unknown. Another class of controlled substances worth our attention are the sedative-hypnotics. Despite the high rates of psychiatric disorders in the cancer population, there is little research into the rates of persistent sedative-hypnotic use in these patients.”
With this in mind, Dr. Cogan and colleagues analyzed MarketScan health care claims data for patients who underwent mastectomy and reconstruction (whether therapeutic or prophylactic) between 2008 and 2017.
The researchers then identified prescription claims for opioids and sedative-hypnotics during three periods:
- Preoperative period – 365 days to 31 days before surgery.
- Perioperative period – 31 days before to 90 days after surgery.
- Postoperative period – 90 days to 365 days after surgery.
‘Striking’ results
Analyses were based on 25,270 women who were not prior users of opioids and 27,651 women who were not prior users of sedative-hypnotics.
Women were considered new persistent substance users if they had no use in the preoperative period but filled at least one prescription in the perioperative period and at least two in the postoperative period.
Overall, 13.1% of opioid-naive patients became persistent opioid users, and 6.6% of sedative-hypnotic-naive patients became persistent sedative-hypnotic users after their mastectomy and reconstruction.
Proportions of substance use were even higher, 17.5% for opioids and 17.0% for sedative-hypnotics, after excluding women who did not receive or fill a perioperative prescription.
In multivariate analysis, patients were significantly more likely to become new persistent opioid users if they had Medicaid insurance (odds ratio, 2.31), had a breast cancer diagnosis vs a prophylactic indication (OR, 1.44), received chemotherapy (OR, 1.33), and were 50-64 years of age (OR, 1.29) or 49 years or younger (OR, 1.27), compared with 65 years or older.
Similarly, patients were significantly more likely to become new persistent sedative-hypnotic users if they received chemotherapy (OR, 2.24), had Medicaid insurance (OR, 1.85), had a breast cancer diagnosis (OR, 1.79), and were 50 to 64 years (OR, 1.65) or 49 years or younger (OR, 1.79).
Finally, patients’ likelihood of new persistent use increased with their number of risk factors. For persistent opioid use, the odds ratio rose from 2.27 in patients with two risk factors to 6.34 in those with five risk factors. For persistent sedative-hypnotic use, the odds ratio rose from 2.55 to 7.71, respectively.
The observed incidences of new persistent substance use in this patient population are “striking,” according to Dr. Cogan. Although the identified risk factors can help providers spot patients who should be monitored more closely, a proactive, systematic approach to postoperative follow-up for all patients is likely needed.
“When you are seeing patients in follow-up, this is something that you might want to explicitly ask about, for example, and not just assume that the postoperative opioids were taken and then disposed of,” Dr. Cogan recommended. “Ask them, ‘Are you still taking opioids, are you still taking your Ambien or whatever medication you were prescribed?’ That’s something to diligently follow up on and make sure the drug is disposed of, or if it somebody is still taking it, refer them for the appropriate services.”
In addition, patients should be encouraged to use over-the-counter medications as much as possible, he advised.
Prescribing: It’s complicated
“I wonder if perhaps we should not be giving opioids at all to certain patients. For example, a mastectomy and implant reconstruction, oftentimes, surprisingly, that’s not a terribly painful procedure. But a TRAM [transverse rectus abdominis] flap or abdominal flap, that really is,” commented press conference comoderator C. Kent Osborne, MD, of Baylor College of Medicine in Houston.
“I’ve been surprised that a lot of my patients get the prescription, but they don’t even use the pills, and I wonder if the prescription is given just so that we’re not bothered at nighttime by somebody calling with pain,” Dr. Osbourne added.
Prescribing opioids for postoperative pain is complicated, Dr. Cogan said, noting that the study did not assess the specific type of reconstruction patients had.
“You don’t want people in pain. Even if they need just one or two pills, it’s still reasonable for them to have it, and we certainly don’t want to imply from our study that people shouldn’t be getting these prescriptions if they need them,” Dr. Cogan elaborated. “But once patients have them, don’t just leave them there in their home because other studies have shown that that’s when people really get addicted to these medications, when they use them later on for other reasons, or they keep using them just because they have them around.”
The risk for persistent use of controlled substances “is something that all physicians need to be aware of for their patients. This is something that we are missing,” maintained press conference comoderator Virginia Kaklamani, MD, DSc, of UT Health San Antonio.
“It’s easy to just give a prescription instead of arguing with a patient about why you are not going to give them a prescription,” Dr. Kaklamani said. “And ultimately ... pain is subjective. If a patient tells you they are in pain, you are, quote-endquote, a bad physician if you tell them they should not be in pain.”
“We need to focus on other ways to deal with the pain, like physical therapy, sending patients to physical medicine and rehab physicians who are trained to help with symptoms from the surgery, with range of motion and all that; that can help with pain,” she recommended. “It’s much harder to do that, right, than to send a prescription in for a narcotic? But that easy answer is always the worst answer.”
This study was funded by the Breast Cancer Research Foundation and the National Institutes of Health. Dr. Cogan declared no conflicts of interest. Dr. Osborne disclosed relationships with Wolters Kluwer, Lilly, Tolmar, and GeneTex. Dr. Kaklamani disclosed relationships with Amgen, AstraZeneca, Athenex, Celgene, Celldex, Daiichi, Eisai, Genentech, Genomic Health, Immunomedics, Novartis, Pfizer, Puma, and Seattle Genetics.
SOURCE: Cogan JC et al. SABCS 2020, Abstract GS3-08.
After their surgery, 13.1% of opioid-naive patients become new persistent opioid users, and 6.6% of sedative-hypnotic–naive patients become new persistent users of sedative-hypnotics. Risk factors for persistent substance use included younger age, a breast cancer diagnosis, and chemotherapy.
“As the opioid epidemic in the United States continues, the rate of opioid dependence in the cancer population continues to increase as well,” study investigator Jacob Cogan, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York, said during a press conference.
“The perioperative period is one of high risk for cancer patients, with up to 10% becoming new persistent opioid users after cancer-related surgery. The rates surrounding mastectomy and reconstruction, however, are unknown. Another class of controlled substances worth our attention are the sedative-hypnotics. Despite the high rates of psychiatric disorders in the cancer population, there is little research into the rates of persistent sedative-hypnotic use in these patients.”
With this in mind, Dr. Cogan and colleagues analyzed MarketScan health care claims data for patients who underwent mastectomy and reconstruction (whether therapeutic or prophylactic) between 2008 and 2017.
The researchers then identified prescription claims for opioids and sedative-hypnotics during three periods:
- Preoperative period – 365 days to 31 days before surgery.
- Perioperative period – 31 days before to 90 days after surgery.
- Postoperative period – 90 days to 365 days after surgery.
‘Striking’ results
Analyses were based on 25,270 women who were not prior users of opioids and 27,651 women who were not prior users of sedative-hypnotics.
Women were considered new persistent substance users if they had no use in the preoperative period but filled at least one prescription in the perioperative period and at least two in the postoperative period.
Overall, 13.1% of opioid-naive patients became persistent opioid users, and 6.6% of sedative-hypnotic-naive patients became persistent sedative-hypnotic users after their mastectomy and reconstruction.
Proportions of substance use were even higher, 17.5% for opioids and 17.0% for sedative-hypnotics, after excluding women who did not receive or fill a perioperative prescription.
In multivariate analysis, patients were significantly more likely to become new persistent opioid users if they had Medicaid insurance (odds ratio, 2.31), had a breast cancer diagnosis vs a prophylactic indication (OR, 1.44), received chemotherapy (OR, 1.33), and were 50-64 years of age (OR, 1.29) or 49 years or younger (OR, 1.27), compared with 65 years or older.
Similarly, patients were significantly more likely to become new persistent sedative-hypnotic users if they received chemotherapy (OR, 2.24), had Medicaid insurance (OR, 1.85), had a breast cancer diagnosis (OR, 1.79), and were 50 to 64 years (OR, 1.65) or 49 years or younger (OR, 1.79).
Finally, patients’ likelihood of new persistent use increased with their number of risk factors. For persistent opioid use, the odds ratio rose from 2.27 in patients with two risk factors to 6.34 in those with five risk factors. For persistent sedative-hypnotic use, the odds ratio rose from 2.55 to 7.71, respectively.
The observed incidences of new persistent substance use in this patient population are “striking,” according to Dr. Cogan. Although the identified risk factors can help providers spot patients who should be monitored more closely, a proactive, systematic approach to postoperative follow-up for all patients is likely needed.
“When you are seeing patients in follow-up, this is something that you might want to explicitly ask about, for example, and not just assume that the postoperative opioids were taken and then disposed of,” Dr. Cogan recommended. “Ask them, ‘Are you still taking opioids, are you still taking your Ambien or whatever medication you were prescribed?’ That’s something to diligently follow up on and make sure the drug is disposed of, or if it somebody is still taking it, refer them for the appropriate services.”
In addition, patients should be encouraged to use over-the-counter medications as much as possible, he advised.
Prescribing: It’s complicated
“I wonder if perhaps we should not be giving opioids at all to certain patients. For example, a mastectomy and implant reconstruction, oftentimes, surprisingly, that’s not a terribly painful procedure. But a TRAM [transverse rectus abdominis] flap or abdominal flap, that really is,” commented press conference comoderator C. Kent Osborne, MD, of Baylor College of Medicine in Houston.
“I’ve been surprised that a lot of my patients get the prescription, but they don’t even use the pills, and I wonder if the prescription is given just so that we’re not bothered at nighttime by somebody calling with pain,” Dr. Osbourne added.
Prescribing opioids for postoperative pain is complicated, Dr. Cogan said, noting that the study did not assess the specific type of reconstruction patients had.
“You don’t want people in pain. Even if they need just one or two pills, it’s still reasonable for them to have it, and we certainly don’t want to imply from our study that people shouldn’t be getting these prescriptions if they need them,” Dr. Cogan elaborated. “But once patients have them, don’t just leave them there in their home because other studies have shown that that’s when people really get addicted to these medications, when they use them later on for other reasons, or they keep using them just because they have them around.”
The risk for persistent use of controlled substances “is something that all physicians need to be aware of for their patients. This is something that we are missing,” maintained press conference comoderator Virginia Kaklamani, MD, DSc, of UT Health San Antonio.
“It’s easy to just give a prescription instead of arguing with a patient about why you are not going to give them a prescription,” Dr. Kaklamani said. “And ultimately ... pain is subjective. If a patient tells you they are in pain, you are, quote-endquote, a bad physician if you tell them they should not be in pain.”
“We need to focus on other ways to deal with the pain, like physical therapy, sending patients to physical medicine and rehab physicians who are trained to help with symptoms from the surgery, with range of motion and all that; that can help with pain,” she recommended. “It’s much harder to do that, right, than to send a prescription in for a narcotic? But that easy answer is always the worst answer.”
This study was funded by the Breast Cancer Research Foundation and the National Institutes of Health. Dr. Cogan declared no conflicts of interest. Dr. Osborne disclosed relationships with Wolters Kluwer, Lilly, Tolmar, and GeneTex. Dr. Kaklamani disclosed relationships with Amgen, AstraZeneca, Athenex, Celgene, Celldex, Daiichi, Eisai, Genentech, Genomic Health, Immunomedics, Novartis, Pfizer, Puma, and Seattle Genetics.
SOURCE: Cogan JC et al. SABCS 2020, Abstract GS3-08.
FROM SABCS 2020
CTCs predict overall survival in metastatic breast cancer
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
FROM SABCS 2020
SABCS 2020: What’s hot, including a major chemotherapy trial
That’s the word from Virginia Kaklamani, MD, from the University of Texas Health Sciences Center San Antonio. Dr. Kaklamani, a professor of medicine in the division of hematology/oncology, is codirector of the meeting that runs online Dec. 8-11.
If the new trial sounds familiar, that’s because it’s a lot like the TAILORx trial, the results of which were first presented in 2018 and have changed practice in women with early-stage disease and no lymph node involvement.
“This is the lymph-node positive TAILORx. It’s extremely important,” Dr. Kaklamani said in an interview, adding that both trials involved women with hormone receptor (HR)–positive, HER2-negative disease.
If the RxPONDER trial shows similar outcomes between women randomized to adjuvant endocrine therapy alone versus endocrine therapy plus chemotherapy, then clinicians “can potentially avoid giving chemotherapy to a large number of women who are currently receiving it,” she explained.
Because women with nodal involvement (one to three positive axillary nodes) are at a higher risk of recurrence, RxPONDER may provide needed insight on the management of these types of breast cancers, Dr. Kaklamani suggested.
Both trials have used the 21-tumor gene expression assay (Oncotype Dx) to determine recurrence-risk status.
Dr. Kaklamani also spotlighted the phase 3 CONTESSA trial (abstract GS4-01) in 600+ patients with locally advanced or metastatic breast cancer that is HR positive and HER2 negative and has been previously treated with a taxane.
The trial features an experimental oral taxane, tesetaxel. The primary objective is to compare the efficacy of tesetaxel plus a reduced dose of capecitabine (Xeloda) versus the approved dose of capecitabine alone. Presented data will include progression-free survival results, indicating about a 3-month PFS advantage with tesetaxel, which is taken once every 3 weeks.
“Oral drugs are convenient for patients and, despite limitations, they are, all in all, a revolution in cancer treatment,” noted Dr. Kaklamani, adding that they beneficially eliminate the need for time-consuming infusions and related clinic visits as well as drug ports.
It will be interesting to see what Steven Vogl, MD, a private practitioner in New Yorky, has to say about CONTESSA and the rest of the SABCS.
He is usually a commentator from the meeting floor, whose self-introduction, “Vogl, New York,” is well known to perennial meeting attendees, according to a profile piece published some years ago.
This year the medical oncologist will also serve as the chair of the “View from the Trenches” session, which is devoted to summarizing the meeting’s most important findings for everyday practitioners.
A number of years ago, Dr. Vogl proposed the idea of this where-the-rubber-meets-the-road session to SABCS meeting planners, which they then adopted. This year, Dr. Kaklamani invited Dr. Vogl to run the session and he accepted.
Dr. Vogl is a “really smart guy who is always right on” with his comments and questions, and he will be the first-ever independent, community-based oncologist to chair a meeting session, said Dr. Kaklamani.
Other hot topics
Another hot topic featured at the meeting will be the use of CDK4/6 inhibitors in the adjuvant treatment of HR-positive and HER2-negative disease that has a high risk of recurrence, Dr. Kaklamani said. New data from two trials, monarchE and PENELOPE-B, will be presented.
First, there will be an update from the monarchE trial (abstract GS1-01). The first results from this trial were reported in September at the European Society for Medical Oncology Virtual Congress 2020. They showed that adding abemaciclib (Verzenio) to endocrine therapy reduced the risk of early recurrence. The positive outcome represented the first treatment improvement in this high-risk setting in more than 20 years, according to experts.
A similar trial, PENELOPE-B (abstract GS1-02), looks at palbociclib (Ibrance) in a somewhat different population – those patients with high relapse risk after neoadjuvant chemotherapy. “These are even higher risk ER+ patients [than those in monarchE], which is why they received chemotherapy before surgery,” commented Dr. Kaklamani.
In triple-negative disease, there will be overall survival (OS) results from the phase 3 KEYNOTE-355 study (abstract GS3-01) of pembrolizumab (Keytruda) versus placebo (plus chemotherapy for all patients) as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. “It’s potentially a huge deal,” said Dr. Kaklamani about the OS data, if they are statistically significant.
A meta-analysis (abstract GS4-08) of data on circulating tumor cells (CTCs), which are shed from the primary tumor into the bloodstream, may point to their value as a tool to determine whether or not a breast cancer treatment is effective. “CTCs allow you to assess how a treatment is doing before you do scans, which typically occur 3 months or so later,” explained Dr. Kaklamani.
CTC results can be assessed in 3-4 weeks and allow clinicians to change treatments if CTC volume increases. However, a previous study of CTCs did not show a clinical benefit with the tool among patients treated mainly with chemotherapies. What’s different about the new study, which is from an international group of investigators, is in the treatments patients with metastatic breast cancer received. “This study is from a different era – with targeted therapies,” said Dr. Kaklamani.
In the new study, changes in CTC levels (with a reduction being a good result) between baseline (pretreatment) and follow-up were analyzed to determine whether they were associated with overall survival.
COVID sessions
On the meeting’s first day, SABCS will feature a special session on COVID-19 and breast cancer. The meeting organizers sought to separate the wheat from the chaff in this subject, as much has already been written, published, or presented.
“We received a lot of abstracts on COVID that were studies that were poorly done. We tried to tease through them and select the well-researched ones,” acknowledged Dr. Kaklamani.
The organizers included two patient advocates who have had COVID-19, including during treatment for breast cancer, as participants in the meeting session. The session will also feature global perspectives, with presenters from Brazil, Italy, and the Netherlands.
Plenary lectures
The meeting’s two plenary lectures will focus, respectively, on the increasingly used clinical approach of neoadjuvant therapy in breast cancer, and research in the time of a pandemic.
Elizabeth Mittendorf, MD, PhD, a surgical oncologist and director of the Breast lmmuno-Oncology program and co-director of the Breast Cancer Clinical Research Program at the Dana-Farber/Brigham and Women’s Cancer Center, Boston, will present “Local regional management following neoadjuvant therapy: Minding the knowledge gaps.”
Ned Sharpless, MD, director of the National Cancer Institute, will present “Advancing cancer research during challenging times.”
Dr. Kaklamani disclosed recieving consulting fees with Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; receiving fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and contracted research with Eisai.
This article first appeared on Medscape.com.
That’s the word from Virginia Kaklamani, MD, from the University of Texas Health Sciences Center San Antonio. Dr. Kaklamani, a professor of medicine in the division of hematology/oncology, is codirector of the meeting that runs online Dec. 8-11.
If the new trial sounds familiar, that’s because it’s a lot like the TAILORx trial, the results of which were first presented in 2018 and have changed practice in women with early-stage disease and no lymph node involvement.
“This is the lymph-node positive TAILORx. It’s extremely important,” Dr. Kaklamani said in an interview, adding that both trials involved women with hormone receptor (HR)–positive, HER2-negative disease.
If the RxPONDER trial shows similar outcomes between women randomized to adjuvant endocrine therapy alone versus endocrine therapy plus chemotherapy, then clinicians “can potentially avoid giving chemotherapy to a large number of women who are currently receiving it,” she explained.
Because women with nodal involvement (one to three positive axillary nodes) are at a higher risk of recurrence, RxPONDER may provide needed insight on the management of these types of breast cancers, Dr. Kaklamani suggested.
Both trials have used the 21-tumor gene expression assay (Oncotype Dx) to determine recurrence-risk status.
Dr. Kaklamani also spotlighted the phase 3 CONTESSA trial (abstract GS4-01) in 600+ patients with locally advanced or metastatic breast cancer that is HR positive and HER2 negative and has been previously treated with a taxane.
The trial features an experimental oral taxane, tesetaxel. The primary objective is to compare the efficacy of tesetaxel plus a reduced dose of capecitabine (Xeloda) versus the approved dose of capecitabine alone. Presented data will include progression-free survival results, indicating about a 3-month PFS advantage with tesetaxel, which is taken once every 3 weeks.
“Oral drugs are convenient for patients and, despite limitations, they are, all in all, a revolution in cancer treatment,” noted Dr. Kaklamani, adding that they beneficially eliminate the need for time-consuming infusions and related clinic visits as well as drug ports.
It will be interesting to see what Steven Vogl, MD, a private practitioner in New Yorky, has to say about CONTESSA and the rest of the SABCS.
He is usually a commentator from the meeting floor, whose self-introduction, “Vogl, New York,” is well known to perennial meeting attendees, according to a profile piece published some years ago.
This year the medical oncologist will also serve as the chair of the “View from the Trenches” session, which is devoted to summarizing the meeting’s most important findings for everyday practitioners.
A number of years ago, Dr. Vogl proposed the idea of this where-the-rubber-meets-the-road session to SABCS meeting planners, which they then adopted. This year, Dr. Kaklamani invited Dr. Vogl to run the session and he accepted.
Dr. Vogl is a “really smart guy who is always right on” with his comments and questions, and he will be the first-ever independent, community-based oncologist to chair a meeting session, said Dr. Kaklamani.
Other hot topics
Another hot topic featured at the meeting will be the use of CDK4/6 inhibitors in the adjuvant treatment of HR-positive and HER2-negative disease that has a high risk of recurrence, Dr. Kaklamani said. New data from two trials, monarchE and PENELOPE-B, will be presented.
First, there will be an update from the monarchE trial (abstract GS1-01). The first results from this trial were reported in September at the European Society for Medical Oncology Virtual Congress 2020. They showed that adding abemaciclib (Verzenio) to endocrine therapy reduced the risk of early recurrence. The positive outcome represented the first treatment improvement in this high-risk setting in more than 20 years, according to experts.
A similar trial, PENELOPE-B (abstract GS1-02), looks at palbociclib (Ibrance) in a somewhat different population – those patients with high relapse risk after neoadjuvant chemotherapy. “These are even higher risk ER+ patients [than those in monarchE], which is why they received chemotherapy before surgery,” commented Dr. Kaklamani.
In triple-negative disease, there will be overall survival (OS) results from the phase 3 KEYNOTE-355 study (abstract GS3-01) of pembrolizumab (Keytruda) versus placebo (plus chemotherapy for all patients) as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. “It’s potentially a huge deal,” said Dr. Kaklamani about the OS data, if they are statistically significant.
A meta-analysis (abstract GS4-08) of data on circulating tumor cells (CTCs), which are shed from the primary tumor into the bloodstream, may point to their value as a tool to determine whether or not a breast cancer treatment is effective. “CTCs allow you to assess how a treatment is doing before you do scans, which typically occur 3 months or so later,” explained Dr. Kaklamani.
CTC results can be assessed in 3-4 weeks and allow clinicians to change treatments if CTC volume increases. However, a previous study of CTCs did not show a clinical benefit with the tool among patients treated mainly with chemotherapies. What’s different about the new study, which is from an international group of investigators, is in the treatments patients with metastatic breast cancer received. “This study is from a different era – with targeted therapies,” said Dr. Kaklamani.
In the new study, changes in CTC levels (with a reduction being a good result) between baseline (pretreatment) and follow-up were analyzed to determine whether they were associated with overall survival.
COVID sessions
On the meeting’s first day, SABCS will feature a special session on COVID-19 and breast cancer. The meeting organizers sought to separate the wheat from the chaff in this subject, as much has already been written, published, or presented.
“We received a lot of abstracts on COVID that were studies that were poorly done. We tried to tease through them and select the well-researched ones,” acknowledged Dr. Kaklamani.
The organizers included two patient advocates who have had COVID-19, including during treatment for breast cancer, as participants in the meeting session. The session will also feature global perspectives, with presenters from Brazil, Italy, and the Netherlands.
Plenary lectures
The meeting’s two plenary lectures will focus, respectively, on the increasingly used clinical approach of neoadjuvant therapy in breast cancer, and research in the time of a pandemic.
Elizabeth Mittendorf, MD, PhD, a surgical oncologist and director of the Breast lmmuno-Oncology program and co-director of the Breast Cancer Clinical Research Program at the Dana-Farber/Brigham and Women’s Cancer Center, Boston, will present “Local regional management following neoadjuvant therapy: Minding the knowledge gaps.”
Ned Sharpless, MD, director of the National Cancer Institute, will present “Advancing cancer research during challenging times.”
Dr. Kaklamani disclosed recieving consulting fees with Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; receiving fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and contracted research with Eisai.
This article first appeared on Medscape.com.
That’s the word from Virginia Kaklamani, MD, from the University of Texas Health Sciences Center San Antonio. Dr. Kaklamani, a professor of medicine in the division of hematology/oncology, is codirector of the meeting that runs online Dec. 8-11.
If the new trial sounds familiar, that’s because it’s a lot like the TAILORx trial, the results of which were first presented in 2018 and have changed practice in women with early-stage disease and no lymph node involvement.
“This is the lymph-node positive TAILORx. It’s extremely important,” Dr. Kaklamani said in an interview, adding that both trials involved women with hormone receptor (HR)–positive, HER2-negative disease.
If the RxPONDER trial shows similar outcomes between women randomized to adjuvant endocrine therapy alone versus endocrine therapy plus chemotherapy, then clinicians “can potentially avoid giving chemotherapy to a large number of women who are currently receiving it,” she explained.
Because women with nodal involvement (one to three positive axillary nodes) are at a higher risk of recurrence, RxPONDER may provide needed insight on the management of these types of breast cancers, Dr. Kaklamani suggested.
Both trials have used the 21-tumor gene expression assay (Oncotype Dx) to determine recurrence-risk status.
Dr. Kaklamani also spotlighted the phase 3 CONTESSA trial (abstract GS4-01) in 600+ patients with locally advanced or metastatic breast cancer that is HR positive and HER2 negative and has been previously treated with a taxane.
The trial features an experimental oral taxane, tesetaxel. The primary objective is to compare the efficacy of tesetaxel plus a reduced dose of capecitabine (Xeloda) versus the approved dose of capecitabine alone. Presented data will include progression-free survival results, indicating about a 3-month PFS advantage with tesetaxel, which is taken once every 3 weeks.
“Oral drugs are convenient for patients and, despite limitations, they are, all in all, a revolution in cancer treatment,” noted Dr. Kaklamani, adding that they beneficially eliminate the need for time-consuming infusions and related clinic visits as well as drug ports.
It will be interesting to see what Steven Vogl, MD, a private practitioner in New Yorky, has to say about CONTESSA and the rest of the SABCS.
He is usually a commentator from the meeting floor, whose self-introduction, “Vogl, New York,” is well known to perennial meeting attendees, according to a profile piece published some years ago.
This year the medical oncologist will also serve as the chair of the “View from the Trenches” session, which is devoted to summarizing the meeting’s most important findings for everyday practitioners.
A number of years ago, Dr. Vogl proposed the idea of this where-the-rubber-meets-the-road session to SABCS meeting planners, which they then adopted. This year, Dr. Kaklamani invited Dr. Vogl to run the session and he accepted.
Dr. Vogl is a “really smart guy who is always right on” with his comments and questions, and he will be the first-ever independent, community-based oncologist to chair a meeting session, said Dr. Kaklamani.
Other hot topics
Another hot topic featured at the meeting will be the use of CDK4/6 inhibitors in the adjuvant treatment of HR-positive and HER2-negative disease that has a high risk of recurrence, Dr. Kaklamani said. New data from two trials, monarchE and PENELOPE-B, will be presented.
First, there will be an update from the monarchE trial (abstract GS1-01). The first results from this trial were reported in September at the European Society for Medical Oncology Virtual Congress 2020. They showed that adding abemaciclib (Verzenio) to endocrine therapy reduced the risk of early recurrence. The positive outcome represented the first treatment improvement in this high-risk setting in more than 20 years, according to experts.
A similar trial, PENELOPE-B (abstract GS1-02), looks at palbociclib (Ibrance) in a somewhat different population – those patients with high relapse risk after neoadjuvant chemotherapy. “These are even higher risk ER+ patients [than those in monarchE], which is why they received chemotherapy before surgery,” commented Dr. Kaklamani.
In triple-negative disease, there will be overall survival (OS) results from the phase 3 KEYNOTE-355 study (abstract GS3-01) of pembrolizumab (Keytruda) versus placebo (plus chemotherapy for all patients) as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. “It’s potentially a huge deal,” said Dr. Kaklamani about the OS data, if they are statistically significant.
A meta-analysis (abstract GS4-08) of data on circulating tumor cells (CTCs), which are shed from the primary tumor into the bloodstream, may point to their value as a tool to determine whether or not a breast cancer treatment is effective. “CTCs allow you to assess how a treatment is doing before you do scans, which typically occur 3 months or so later,” explained Dr. Kaklamani.
CTC results can be assessed in 3-4 weeks and allow clinicians to change treatments if CTC volume increases. However, a previous study of CTCs did not show a clinical benefit with the tool among patients treated mainly with chemotherapies. What’s different about the new study, which is from an international group of investigators, is in the treatments patients with metastatic breast cancer received. “This study is from a different era – with targeted therapies,” said Dr. Kaklamani.
In the new study, changes in CTC levels (with a reduction being a good result) between baseline (pretreatment) and follow-up were analyzed to determine whether they were associated with overall survival.
COVID sessions
On the meeting’s first day, SABCS will feature a special session on COVID-19 and breast cancer. The meeting organizers sought to separate the wheat from the chaff in this subject, as much has already been written, published, or presented.
“We received a lot of abstracts on COVID that were studies that were poorly done. We tried to tease through them and select the well-researched ones,” acknowledged Dr. Kaklamani.
The organizers included two patient advocates who have had COVID-19, including during treatment for breast cancer, as participants in the meeting session. The session will also feature global perspectives, with presenters from Brazil, Italy, and the Netherlands.
Plenary lectures
The meeting’s two plenary lectures will focus, respectively, on the increasingly used clinical approach of neoadjuvant therapy in breast cancer, and research in the time of a pandemic.
Elizabeth Mittendorf, MD, PhD, a surgical oncologist and director of the Breast lmmuno-Oncology program and co-director of the Breast Cancer Clinical Research Program at the Dana-Farber/Brigham and Women’s Cancer Center, Boston, will present “Local regional management following neoadjuvant therapy: Minding the knowledge gaps.”
Ned Sharpless, MD, director of the National Cancer Institute, will present “Advancing cancer research during challenging times.”
Dr. Kaklamani disclosed recieving consulting fees with Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; receiving fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and contracted research with Eisai.
This article first appeared on Medscape.com.
FROM SABCS 2020