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Oral SERD camizestrant prolongs PFS vs. fulvestrant in breast cancer
SAN ANTONIO – compared with the first-generation SERD fulvestrant Faslodex, in the SERENA-2 trial, shows a study recently presented at the San Antonio Breast Cancer Symposium.
Among 180 postmenopausal women with ER+/HER2– breast cancers that had recurred or progressed following at least one line of endocrine therapy, the median progression-free survival (PFS) after a median follow-up of 16.6-17.4 months was 7.2 months for patients treated at a 75-mg dose of camizestrant and 7.7 months for those treated at a 150-mg dose, compared with 3.7 months for patients who received fulvestrant, reported Mafalda Oliveira, MD, PhD, from Vall d’Hebron University Hospital in Barcelona.
Oral agent
Camizestrant is a next-generation oral SERD and pure estrogen receptor antagonist that was shown in the SERENA-1 trial to be safe and to have clinical activity against ER+ breast cancers.
SERENA-2 pitted camizestrant at doses of 75 mg, 150 mg, or 300 mg against standard-dose fulvestrant, although the 300-mg dose was dropped in a protocol amendment after 20 patients had been assigned to that arm. (Currently planned studies with camizestrant will be conducted with the 75-mg dose.)
The investigators enrolled women with ER+/HER2– advanced breast cancer who had not previously received fulvestrant or an oral SERD. Eligible patients were limited to no more than one prior line of endocrine and one prior line of chemotherapy for advanced breast cancers. The study included patients with both measurable and unmeasurable disease.
The median patient age was about 60 years. Approximately 59% of patients in each arm had either lung or liver metastases. Patients with recurrence in bone only comprised 14.9%-19.4%.
Mutations in ESR1, a gene associated with hormonal resistance, were detectable in 29.7%-47.9% of patients.
Better PFS
As noted before, the primary endpoint of investigator-assessed median PFS favored camizestrant in both the 75-mg arm (7.2 months) and the 150-mg arm (7.7 months), with respective adjusted hazard ratios for progression versus fulvestrant of 0.58 (P = .0124) and 0.67 (P = .0161).
Camizestrant at the 75-mg dose was also superior to fulvestrant among patients who had previously received a cyclin-dependent kinase 4/6 inhibitor, with median PFS of 5.5 months and 3.8 months for the 75-mg and 150-mg doses, respectively, compared with 2.1 months.
The adjusted HR for progression with camizestrant with the 75-mg dose was 0.49, with a 90% confidence interval indicating significance. The 150-mg dose was not significantly superior to fulvestrant, however.
Both camizestrant doses were also superior for prolonging PFS versus fulvestrant among patients with lung and/or liver metastases, with median PFS of 7.2 months, 5.6 months, and 2.0 months, respectively.
The experimental SERD also outperformed fulvestrant in an analysis looking at PFS by ESR1 mutational status and ER-driven disease. Among patients with ESR1 wild type, however, median PFS rates with camizestrant 75 mg and fulvestrant were the same (7.2 months).
The 24-week objective response rates were 15.7% in the 75-mg camizestrant arm, 20% in the 150-mg arm, and 11.8% in the fulvestrant arm. The respective clinical benefit rates, including all patients with responses or stable disease, were 47.3%, 49.3%, and 38.4%. The camizestrant clinical benefit rates did not differ significantly from those with fulvestrant, however.
Treatment-related adverse events of grade 3 or greater occurred in only five patients, and only two patients, both in the 75-mg camizestrant arm, discontinued therapy because of adverse events. There were no treatment-related deaths.
Adverse events that occurred only with camizestrant included photopsia (flashing lights or floaters in the field of vision) and sinus bradycardia.
Promising, but early
Carlos Artega, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, who was not involved in the study, said the data look promising in comparison with fulvestrant.
“There is a clear suggestion that this might be better,” he said. “[Camizestrant] seems to be better at reducing the titer in plasma of the ESR1 mutation, and there is very strong basic science that supports that.”
He noted that the study numbers were relatively small, however.
Dr. Arteaga was speaking at a media briefing held immediately prior to the presentation of the data in an oral abstract session.
Fabrice Andre, MD, from Gustave Roussy in Villejuif, France, the invited discussant for the oral session, noted that, in patients with ESR1 wild type, where fulvestrant shows some efficacy, camizestrant appears to be equally effective, and that the latter agent may be more synergistic with targeted therapies than fulvestrant.
Given high patient dropout rates with currently available SERDs, there is a need for SERDs used in the adjuvant setting that are effective at minimally bioactive doses for patients who are predicted to poorly adherent, Dr. Andre said.
The study was funded by AstraZeneca. Dr. Oliveira has received personal funding from AstraZeneca, Guardant Health, Roche, Merck Sharp & Dohme, Pfizer, Seagen, iTeos Therapeutics, Eisai, Novartis, Relay Therapeutics, and Gilead. Dr. Arteaga is a scientific adviser to AstraZeneca and others, and has received grant support from Pfizer Lilly and Takeda. Dr. Andre disclosed fees to his hospital on his behalf from AstraZeneca, Daiichi Sankyo, Sanofi, Pfizer, Lilly, and Roche.
SAN ANTONIO – compared with the first-generation SERD fulvestrant Faslodex, in the SERENA-2 trial, shows a study recently presented at the San Antonio Breast Cancer Symposium.
Among 180 postmenopausal women with ER+/HER2– breast cancers that had recurred or progressed following at least one line of endocrine therapy, the median progression-free survival (PFS) after a median follow-up of 16.6-17.4 months was 7.2 months for patients treated at a 75-mg dose of camizestrant and 7.7 months for those treated at a 150-mg dose, compared with 3.7 months for patients who received fulvestrant, reported Mafalda Oliveira, MD, PhD, from Vall d’Hebron University Hospital in Barcelona.
Oral agent
Camizestrant is a next-generation oral SERD and pure estrogen receptor antagonist that was shown in the SERENA-1 trial to be safe and to have clinical activity against ER+ breast cancers.
SERENA-2 pitted camizestrant at doses of 75 mg, 150 mg, or 300 mg against standard-dose fulvestrant, although the 300-mg dose was dropped in a protocol amendment after 20 patients had been assigned to that arm. (Currently planned studies with camizestrant will be conducted with the 75-mg dose.)
The investigators enrolled women with ER+/HER2– advanced breast cancer who had not previously received fulvestrant or an oral SERD. Eligible patients were limited to no more than one prior line of endocrine and one prior line of chemotherapy for advanced breast cancers. The study included patients with both measurable and unmeasurable disease.
The median patient age was about 60 years. Approximately 59% of patients in each arm had either lung or liver metastases. Patients with recurrence in bone only comprised 14.9%-19.4%.
Mutations in ESR1, a gene associated with hormonal resistance, were detectable in 29.7%-47.9% of patients.
Better PFS
As noted before, the primary endpoint of investigator-assessed median PFS favored camizestrant in both the 75-mg arm (7.2 months) and the 150-mg arm (7.7 months), with respective adjusted hazard ratios for progression versus fulvestrant of 0.58 (P = .0124) and 0.67 (P = .0161).
Camizestrant at the 75-mg dose was also superior to fulvestrant among patients who had previously received a cyclin-dependent kinase 4/6 inhibitor, with median PFS of 5.5 months and 3.8 months for the 75-mg and 150-mg doses, respectively, compared with 2.1 months.
The adjusted HR for progression with camizestrant with the 75-mg dose was 0.49, with a 90% confidence interval indicating significance. The 150-mg dose was not significantly superior to fulvestrant, however.
Both camizestrant doses were also superior for prolonging PFS versus fulvestrant among patients with lung and/or liver metastases, with median PFS of 7.2 months, 5.6 months, and 2.0 months, respectively.
The experimental SERD also outperformed fulvestrant in an analysis looking at PFS by ESR1 mutational status and ER-driven disease. Among patients with ESR1 wild type, however, median PFS rates with camizestrant 75 mg and fulvestrant were the same (7.2 months).
The 24-week objective response rates were 15.7% in the 75-mg camizestrant arm, 20% in the 150-mg arm, and 11.8% in the fulvestrant arm. The respective clinical benefit rates, including all patients with responses or stable disease, were 47.3%, 49.3%, and 38.4%. The camizestrant clinical benefit rates did not differ significantly from those with fulvestrant, however.
Treatment-related adverse events of grade 3 or greater occurred in only five patients, and only two patients, both in the 75-mg camizestrant arm, discontinued therapy because of adverse events. There were no treatment-related deaths.
Adverse events that occurred only with camizestrant included photopsia (flashing lights or floaters in the field of vision) and sinus bradycardia.
Promising, but early
Carlos Artega, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, who was not involved in the study, said the data look promising in comparison with fulvestrant.
“There is a clear suggestion that this might be better,” he said. “[Camizestrant] seems to be better at reducing the titer in plasma of the ESR1 mutation, and there is very strong basic science that supports that.”
He noted that the study numbers were relatively small, however.
Dr. Arteaga was speaking at a media briefing held immediately prior to the presentation of the data in an oral abstract session.
Fabrice Andre, MD, from Gustave Roussy in Villejuif, France, the invited discussant for the oral session, noted that, in patients with ESR1 wild type, where fulvestrant shows some efficacy, camizestrant appears to be equally effective, and that the latter agent may be more synergistic with targeted therapies than fulvestrant.
Given high patient dropout rates with currently available SERDs, there is a need for SERDs used in the adjuvant setting that are effective at minimally bioactive doses for patients who are predicted to poorly adherent, Dr. Andre said.
The study was funded by AstraZeneca. Dr. Oliveira has received personal funding from AstraZeneca, Guardant Health, Roche, Merck Sharp & Dohme, Pfizer, Seagen, iTeos Therapeutics, Eisai, Novartis, Relay Therapeutics, and Gilead. Dr. Arteaga is a scientific adviser to AstraZeneca and others, and has received grant support from Pfizer Lilly and Takeda. Dr. Andre disclosed fees to his hospital on his behalf from AstraZeneca, Daiichi Sankyo, Sanofi, Pfizer, Lilly, and Roche.
SAN ANTONIO – compared with the first-generation SERD fulvestrant Faslodex, in the SERENA-2 trial, shows a study recently presented at the San Antonio Breast Cancer Symposium.
Among 180 postmenopausal women with ER+/HER2– breast cancers that had recurred or progressed following at least one line of endocrine therapy, the median progression-free survival (PFS) after a median follow-up of 16.6-17.4 months was 7.2 months for patients treated at a 75-mg dose of camizestrant and 7.7 months for those treated at a 150-mg dose, compared with 3.7 months for patients who received fulvestrant, reported Mafalda Oliveira, MD, PhD, from Vall d’Hebron University Hospital in Barcelona.
Oral agent
Camizestrant is a next-generation oral SERD and pure estrogen receptor antagonist that was shown in the SERENA-1 trial to be safe and to have clinical activity against ER+ breast cancers.
SERENA-2 pitted camizestrant at doses of 75 mg, 150 mg, or 300 mg against standard-dose fulvestrant, although the 300-mg dose was dropped in a protocol amendment after 20 patients had been assigned to that arm. (Currently planned studies with camizestrant will be conducted with the 75-mg dose.)
The investigators enrolled women with ER+/HER2– advanced breast cancer who had not previously received fulvestrant or an oral SERD. Eligible patients were limited to no more than one prior line of endocrine and one prior line of chemotherapy for advanced breast cancers. The study included patients with both measurable and unmeasurable disease.
The median patient age was about 60 years. Approximately 59% of patients in each arm had either lung or liver metastases. Patients with recurrence in bone only comprised 14.9%-19.4%.
Mutations in ESR1, a gene associated with hormonal resistance, were detectable in 29.7%-47.9% of patients.
Better PFS
As noted before, the primary endpoint of investigator-assessed median PFS favored camizestrant in both the 75-mg arm (7.2 months) and the 150-mg arm (7.7 months), with respective adjusted hazard ratios for progression versus fulvestrant of 0.58 (P = .0124) and 0.67 (P = .0161).
Camizestrant at the 75-mg dose was also superior to fulvestrant among patients who had previously received a cyclin-dependent kinase 4/6 inhibitor, with median PFS of 5.5 months and 3.8 months for the 75-mg and 150-mg doses, respectively, compared with 2.1 months.
The adjusted HR for progression with camizestrant with the 75-mg dose was 0.49, with a 90% confidence interval indicating significance. The 150-mg dose was not significantly superior to fulvestrant, however.
Both camizestrant doses were also superior for prolonging PFS versus fulvestrant among patients with lung and/or liver metastases, with median PFS of 7.2 months, 5.6 months, and 2.0 months, respectively.
The experimental SERD also outperformed fulvestrant in an analysis looking at PFS by ESR1 mutational status and ER-driven disease. Among patients with ESR1 wild type, however, median PFS rates with camizestrant 75 mg and fulvestrant were the same (7.2 months).
The 24-week objective response rates were 15.7% in the 75-mg camizestrant arm, 20% in the 150-mg arm, and 11.8% in the fulvestrant arm. The respective clinical benefit rates, including all patients with responses or stable disease, were 47.3%, 49.3%, and 38.4%. The camizestrant clinical benefit rates did not differ significantly from those with fulvestrant, however.
Treatment-related adverse events of grade 3 or greater occurred in only five patients, and only two patients, both in the 75-mg camizestrant arm, discontinued therapy because of adverse events. There were no treatment-related deaths.
Adverse events that occurred only with camizestrant included photopsia (flashing lights or floaters in the field of vision) and sinus bradycardia.
Promising, but early
Carlos Artega, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, who was not involved in the study, said the data look promising in comparison with fulvestrant.
“There is a clear suggestion that this might be better,” he said. “[Camizestrant] seems to be better at reducing the titer in plasma of the ESR1 mutation, and there is very strong basic science that supports that.”
He noted that the study numbers were relatively small, however.
Dr. Arteaga was speaking at a media briefing held immediately prior to the presentation of the data in an oral abstract session.
Fabrice Andre, MD, from Gustave Roussy in Villejuif, France, the invited discussant for the oral session, noted that, in patients with ESR1 wild type, where fulvestrant shows some efficacy, camizestrant appears to be equally effective, and that the latter agent may be more synergistic with targeted therapies than fulvestrant.
Given high patient dropout rates with currently available SERDs, there is a need for SERDs used in the adjuvant setting that are effective at minimally bioactive doses for patients who are predicted to poorly adherent, Dr. Andre said.
The study was funded by AstraZeneca. Dr. Oliveira has received personal funding from AstraZeneca, Guardant Health, Roche, Merck Sharp & Dohme, Pfizer, Seagen, iTeos Therapeutics, Eisai, Novartis, Relay Therapeutics, and Gilead. Dr. Arteaga is a scientific adviser to AstraZeneca and others, and has received grant support from Pfizer Lilly and Takeda. Dr. Andre disclosed fees to his hospital on his behalf from AstraZeneca, Daiichi Sankyo, Sanofi, Pfizer, Lilly, and Roche.
AT SABCS 2022
Chemotherapy meets its match against aggressive ER+/HER2– breast cancers
SAN ANTONIO – Results of a study being hailed as practice changing showed that, for pre- or perimenopausal women with aggressive hormone receptor-positive, HER2-negative (HR+/HER2–) untreated breast cancers,
That’s according to investigators of the phase 2 RIGHT Choice study who found that first-line ribociclib, combined with either letrozole or anastrozole plus goserelin, was associated with a doubling of progression-free survival (PFS), compared with the investigator’s choice of combination chemotherapy, reported Yen-Shen Lu, MD, from National Taiwan University Hospital in Taipei, at the San Antonio Breast Cancer Symposium.
“These results from RIGHT Choice have now shown that first-line ribociclib plus endocrine therapy should be considered the preferred treatment option for this patient population,” he said.
Chemo loses its luster
“This is not time first time that we’ve looked at a CDK4/6 inhibitor compared to chemotherapy, but this is the first time that we’ve seen it compared to a combination chemotherapy,” commented Virginia Kaklamani, MD, from University of Texas Health, San Antonio, who moderated a media briefing held prior to Dr. Lu’s presentation of the data in an oral abstract session.
“I think with this study we’re finding that chemotherapy, at least in the early stages of [estrogen receptor]–positive breast cancer, is probably not appropriate for our patients,” she said.
Chemotherapy is the current standard of care for patients with advanced breast cancers with aggressive disease features that can include rapidly progressive disease, high symptom burden, and/or life-threatening visceral crises requiring rapid control of disease, Dr. Lu said.
Compared with single-agent chemotherapy, combination chemotherapy, for those who can tolerate it, is associated with higher overall response rates and longer PFS.
Although ribociclib plus endocrine therapy has been shown to offer significant PFS and overall survival (OS) benefits, compared with endocrine therapy alone, there have not been any head-to-head studies pitting these agents against combination chemotherapy.
Study details
To rectify this, Dr. Lu and colleagues enrolled 222 pre- or perimenopausal women with HR+/HER2– advanced breast cancers with aggressive features who had not yet received systemic therapy for advanced breast cancer.
After stratification for the presence or absence of liver metastases and by length of disease-free interval (time from complete resection of a primary tumor to documented recurrence), the patients were randomly assigned to receive either ribociclib 600 mg 3 weeks on, 1 week off) plus letrozole or anastrozole and goserelin, or the investigators choice of either docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine.
After a median follow-up of 24.1 months at the time of data cutoff in April 2022, median PFS, the primary endpoint, was 24 months in the ribociclib plus endocrine therapy arm versus 12.3 months in the chemotherapy arm.
This translated into a hazard ratio for progression on ribociclib plus endocrine therapy of 0.54 (P = .0007).
The benefit for the ribociclib combination, compared with combination chemotherapy, was consistent across most patient subgroups, Dr. Lu said.
The median time to treatment failure was also longer with ribociclib, at 18.6 months versus 8.5 months, respectively, translating into a HR of 0.45 favoring ribociclib, with a statistically significant confidence interval.
Overall response rates were similar between the groups, at 65.2% with ribociclib versus 60% with chemotherapy. The respective clinical benefit rates (including complete and partial responses plus stable disease) were 80.4% versus 72.7%.
The time to response was similar between the treatment arms, an important consideration for patients with rapidly progressive disease, Dr. Lu noted.
Adverse events that occurred more frequently with ribociclib were neutropenia and leukopenia. Events more common with chemotherapy included anemia, liver enzyme elevations, nausea, vomiting, diarrhea, alopecia, fatigue, and palmar-plantar erythrodysesthesia.
Confirmation
“These data are just confirming what we’ve already known, and that is that with ER-positive, HER2-negative breast cancer where you have metastatic disease and more aggressive characteristics, treating with a CDK4/6 inhibitor and endocrine therapy leads to high response rates,” breast cancer specialist Matthew P. Goetz, MD, from the Mayo Clinic in Rochester, Minn., said in an interview. Dr. Goetz was not involved in the study.
“What was surprising to me was the fact that the response rates with chemotherapy were not higher,” he said. “We sometime think that the more chemotherapy, the higher the response rates. It was nice to see a direct comparison with chemotherapy, and really to see that giving a target therapy actually led to very, very good results. That tells us that there should be very few situations where we would be prescribing chemotherapy over CDK4/6 inhibitor–based therapies.”
The study was funded by Novartis Pharma. Dr. Lu disclosed personal funding from Novartis and others. Dr. Goetz disclosed grants and other supports for work with the development of abemaciclib and palbociclib, and consulting for Pfizer and others. Dr. Kaklamani disclosed speakers bureau activity for Novartis and others, research support from Eisai, and consulting for other companies.
SAN ANTONIO – Results of a study being hailed as practice changing showed that, for pre- or perimenopausal women with aggressive hormone receptor-positive, HER2-negative (HR+/HER2–) untreated breast cancers,
That’s according to investigators of the phase 2 RIGHT Choice study who found that first-line ribociclib, combined with either letrozole or anastrozole plus goserelin, was associated with a doubling of progression-free survival (PFS), compared with the investigator’s choice of combination chemotherapy, reported Yen-Shen Lu, MD, from National Taiwan University Hospital in Taipei, at the San Antonio Breast Cancer Symposium.
“These results from RIGHT Choice have now shown that first-line ribociclib plus endocrine therapy should be considered the preferred treatment option for this patient population,” he said.
Chemo loses its luster
“This is not time first time that we’ve looked at a CDK4/6 inhibitor compared to chemotherapy, but this is the first time that we’ve seen it compared to a combination chemotherapy,” commented Virginia Kaklamani, MD, from University of Texas Health, San Antonio, who moderated a media briefing held prior to Dr. Lu’s presentation of the data in an oral abstract session.
“I think with this study we’re finding that chemotherapy, at least in the early stages of [estrogen receptor]–positive breast cancer, is probably not appropriate for our patients,” she said.
Chemotherapy is the current standard of care for patients with advanced breast cancers with aggressive disease features that can include rapidly progressive disease, high symptom burden, and/or life-threatening visceral crises requiring rapid control of disease, Dr. Lu said.
Compared with single-agent chemotherapy, combination chemotherapy, for those who can tolerate it, is associated with higher overall response rates and longer PFS.
Although ribociclib plus endocrine therapy has been shown to offer significant PFS and overall survival (OS) benefits, compared with endocrine therapy alone, there have not been any head-to-head studies pitting these agents against combination chemotherapy.
Study details
To rectify this, Dr. Lu and colleagues enrolled 222 pre- or perimenopausal women with HR+/HER2– advanced breast cancers with aggressive features who had not yet received systemic therapy for advanced breast cancer.
After stratification for the presence or absence of liver metastases and by length of disease-free interval (time from complete resection of a primary tumor to documented recurrence), the patients were randomly assigned to receive either ribociclib 600 mg 3 weeks on, 1 week off) plus letrozole or anastrozole and goserelin, or the investigators choice of either docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine.
After a median follow-up of 24.1 months at the time of data cutoff in April 2022, median PFS, the primary endpoint, was 24 months in the ribociclib plus endocrine therapy arm versus 12.3 months in the chemotherapy arm.
This translated into a hazard ratio for progression on ribociclib plus endocrine therapy of 0.54 (P = .0007).
The benefit for the ribociclib combination, compared with combination chemotherapy, was consistent across most patient subgroups, Dr. Lu said.
The median time to treatment failure was also longer with ribociclib, at 18.6 months versus 8.5 months, respectively, translating into a HR of 0.45 favoring ribociclib, with a statistically significant confidence interval.
Overall response rates were similar between the groups, at 65.2% with ribociclib versus 60% with chemotherapy. The respective clinical benefit rates (including complete and partial responses plus stable disease) were 80.4% versus 72.7%.
The time to response was similar between the treatment arms, an important consideration for patients with rapidly progressive disease, Dr. Lu noted.
Adverse events that occurred more frequently with ribociclib were neutropenia and leukopenia. Events more common with chemotherapy included anemia, liver enzyme elevations, nausea, vomiting, diarrhea, alopecia, fatigue, and palmar-plantar erythrodysesthesia.
Confirmation
“These data are just confirming what we’ve already known, and that is that with ER-positive, HER2-negative breast cancer where you have metastatic disease and more aggressive characteristics, treating with a CDK4/6 inhibitor and endocrine therapy leads to high response rates,” breast cancer specialist Matthew P. Goetz, MD, from the Mayo Clinic in Rochester, Minn., said in an interview. Dr. Goetz was not involved in the study.
“What was surprising to me was the fact that the response rates with chemotherapy were not higher,” he said. “We sometime think that the more chemotherapy, the higher the response rates. It was nice to see a direct comparison with chemotherapy, and really to see that giving a target therapy actually led to very, very good results. That tells us that there should be very few situations where we would be prescribing chemotherapy over CDK4/6 inhibitor–based therapies.”
The study was funded by Novartis Pharma. Dr. Lu disclosed personal funding from Novartis and others. Dr. Goetz disclosed grants and other supports for work with the development of abemaciclib and palbociclib, and consulting for Pfizer and others. Dr. Kaklamani disclosed speakers bureau activity for Novartis and others, research support from Eisai, and consulting for other companies.
SAN ANTONIO – Results of a study being hailed as practice changing showed that, for pre- or perimenopausal women with aggressive hormone receptor-positive, HER2-negative (HR+/HER2–) untreated breast cancers,
That’s according to investigators of the phase 2 RIGHT Choice study who found that first-line ribociclib, combined with either letrozole or anastrozole plus goserelin, was associated with a doubling of progression-free survival (PFS), compared with the investigator’s choice of combination chemotherapy, reported Yen-Shen Lu, MD, from National Taiwan University Hospital in Taipei, at the San Antonio Breast Cancer Symposium.
“These results from RIGHT Choice have now shown that first-line ribociclib plus endocrine therapy should be considered the preferred treatment option for this patient population,” he said.
Chemo loses its luster
“This is not time first time that we’ve looked at a CDK4/6 inhibitor compared to chemotherapy, but this is the first time that we’ve seen it compared to a combination chemotherapy,” commented Virginia Kaklamani, MD, from University of Texas Health, San Antonio, who moderated a media briefing held prior to Dr. Lu’s presentation of the data in an oral abstract session.
“I think with this study we’re finding that chemotherapy, at least in the early stages of [estrogen receptor]–positive breast cancer, is probably not appropriate for our patients,” she said.
Chemotherapy is the current standard of care for patients with advanced breast cancers with aggressive disease features that can include rapidly progressive disease, high symptom burden, and/or life-threatening visceral crises requiring rapid control of disease, Dr. Lu said.
Compared with single-agent chemotherapy, combination chemotherapy, for those who can tolerate it, is associated with higher overall response rates and longer PFS.
Although ribociclib plus endocrine therapy has been shown to offer significant PFS and overall survival (OS) benefits, compared with endocrine therapy alone, there have not been any head-to-head studies pitting these agents against combination chemotherapy.
Study details
To rectify this, Dr. Lu and colleagues enrolled 222 pre- or perimenopausal women with HR+/HER2– advanced breast cancers with aggressive features who had not yet received systemic therapy for advanced breast cancer.
After stratification for the presence or absence of liver metastases and by length of disease-free interval (time from complete resection of a primary tumor to documented recurrence), the patients were randomly assigned to receive either ribociclib 600 mg 3 weeks on, 1 week off) plus letrozole or anastrozole and goserelin, or the investigators choice of either docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine.
After a median follow-up of 24.1 months at the time of data cutoff in April 2022, median PFS, the primary endpoint, was 24 months in the ribociclib plus endocrine therapy arm versus 12.3 months in the chemotherapy arm.
This translated into a hazard ratio for progression on ribociclib plus endocrine therapy of 0.54 (P = .0007).
The benefit for the ribociclib combination, compared with combination chemotherapy, was consistent across most patient subgroups, Dr. Lu said.
The median time to treatment failure was also longer with ribociclib, at 18.6 months versus 8.5 months, respectively, translating into a HR of 0.45 favoring ribociclib, with a statistically significant confidence interval.
Overall response rates were similar between the groups, at 65.2% with ribociclib versus 60% with chemotherapy. The respective clinical benefit rates (including complete and partial responses plus stable disease) were 80.4% versus 72.7%.
The time to response was similar between the treatment arms, an important consideration for patients with rapidly progressive disease, Dr. Lu noted.
Adverse events that occurred more frequently with ribociclib were neutropenia and leukopenia. Events more common with chemotherapy included anemia, liver enzyme elevations, nausea, vomiting, diarrhea, alopecia, fatigue, and palmar-plantar erythrodysesthesia.
Confirmation
“These data are just confirming what we’ve already known, and that is that with ER-positive, HER2-negative breast cancer where you have metastatic disease and more aggressive characteristics, treating with a CDK4/6 inhibitor and endocrine therapy leads to high response rates,” breast cancer specialist Matthew P. Goetz, MD, from the Mayo Clinic in Rochester, Minn., said in an interview. Dr. Goetz was not involved in the study.
“What was surprising to me was the fact that the response rates with chemotherapy were not higher,” he said. “We sometime think that the more chemotherapy, the higher the response rates. It was nice to see a direct comparison with chemotherapy, and really to see that giving a target therapy actually led to very, very good results. That tells us that there should be very few situations where we would be prescribing chemotherapy over CDK4/6 inhibitor–based therapies.”
The study was funded by Novartis Pharma. Dr. Lu disclosed personal funding from Novartis and others. Dr. Goetz disclosed grants and other supports for work with the development of abemaciclib and palbociclib, and consulting for Pfizer and others. Dr. Kaklamani disclosed speakers bureau activity for Novartis and others, research support from Eisai, and consulting for other companies.
AT SABCS 2022
Potential cause of worse outcomes among Black breast cancer patients found
SAN ANTONIO – compared with White women, a discovery that may at least partially explain racial differences in breast cancer outcomes, investigators say.
The finding, which comes from a retrospective study comparing differences in tumor microenvironment of metastasis (TMEM) “doorways” between Black and White women suggest that tumors in Black women may have a stronger prometastatic response to neoadjuvant chemotherapy than tumors in White women, reported Maja H. Oktay, MD, PhD, of Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, New York, at the San Antonio Breast Cancer Symposium.
“Looking forward ... we propose to use TMEM doorway density as a prognostic marker for distant recurrence-free survival as a marker of dissemination, and also as a predictive marker of response to drugs that can block TMEM doorways,” she said at a briefing held prior to the presentation of data in an oral abstract session.
Entry points
As their name implies, TMEM doorways are transient entry points or portals that allow cancer cells to disseminate to distant sites. TMEM doorways are composed of tumor cells, macrophages, and endothelial cells that come into direct contact and together create temporary vascular openings that allow tumor cells to cross cell walls into circulation, where they can then hitch a ride and travel to distant organ sites.
Previous studies have shown that TMEM doorway density is a prognostic marker of metastasis in breast cancer patients treated with adjuvant chemotherapy. And as Dr. Oktay and colleagues showed in the current study, TMEM doorway density, as measured by a TMEM doorway score, is a prognostic marker for distant metastatic recurrence of ER+/HER2– breast cancer following neoadjuvant chemotherapy.
They also showed that neoadjuvant chemotherapy may increase the TMEM doorway score and lead to a pro–metastatic tumor microenvironment in some women.
Doorway scores
The investigators measured TMEM doorway scores from residual breast cancers in women who had undergone standard neoadjuvant chemotherapy. The cohort consisted of 96 Black women, 43 of whom had ER+/HER2– breast cancer and 37 of whom had triple-negative breast cancer (TNBC), and 87 White women, 50 with ER+/HER2– cancer and 22 with TNBC. The remaining patients had other breast cancer subtypes.
They found that TNBCs had higher TMEM doorway density score and higher macrophage density scores, which may explain why patients with TNBC often have early recurrence of disease.
They also found that, compared with White patients, Black patients with ER+/HER2– tumors, but not TNBC tumors, had higher TMEM doorway density scores. Similarly, Black patients with ER+/HER– cancers, but not TNBC, had higher macrophage levels than White women, a finding that may explain racial disparity in ER+/HER2– disease, Dr. Oktay said.
For the entire cohort, patients with high TMEM doorway density scores had significantly worse distant recurrence–free survival than patients with intermediate or low scores (P = .008), and there was a trend toward worse DRFS among all patients with ER+/HER2– who were in the highest third of scores, but this did not quite reach statistical significance.
High versus low TMEM doorway density score was also an independent prognostic factor for worse outcomes among the entire cohort (P = .01).
There was no significant difference in TMEM density scores among patients with TNBC.
Neither high macrophage counts nor microvascular density alone were significantly associated with inferior DRFS. TMEM doorway score was the only factor significantly prognostic for worse outcomes among patients in the entire cohort.
Hypothesis needs further testing
Invited discussant Lori Pierce, MD, a radiation oncologist with Michigan Medicine, University of Michigan, Ann Arbor, said it’s unclear whether TMEM doorway density changed following neoadjuvant chemotherapy as there were no prechemotherapy scores available in this study.
“But I think the key part is that, if we think neoadjuvant chemotherapy promotes metastasis, then there should be an inferior outcome compared to adjuvant chemotherapy, but that’s not what we see. Well-powered randomized trials show equivalent outcomes with neoadjuvant chemotherapy as well as adjuvant,” she said.
She noted that a 2018 meta-analysis of individual patient data from 10 randomized trials comparing neoadjuvant with adjuvant chemotherapy in early breast cancer showed no differences in long-term distant recurrences, breast cancer–specific mortality, or all-cause mortality between the two modalities.
“While I think these data are very provocative, I certainly wouldn’t want Black women or any women who need neoadjuvant therapy to be discouraged because of these data. We need these data to be tested rigorously, so I look forward to the clinical trials that will test this question and can really give us more information about this very interesting hypothesis,” Dr. Pierce said.
The study was funded by the National Institutes of Health, New York State Department of Health Peter T. Rowley Breast Cancer Scientific Research Projects, Helen & Irving Spatz Family Foundation, Evelyn Gruss Lipper Charitable Foundation, and the Gruss-Lipper Biophotonics Center and the integrated imaging program at the Albert Einstein College of Medicine. Dr. Oktay reported no conflicts of interests.
SAN ANTONIO – compared with White women, a discovery that may at least partially explain racial differences in breast cancer outcomes, investigators say.
The finding, which comes from a retrospective study comparing differences in tumor microenvironment of metastasis (TMEM) “doorways” between Black and White women suggest that tumors in Black women may have a stronger prometastatic response to neoadjuvant chemotherapy than tumors in White women, reported Maja H. Oktay, MD, PhD, of Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, New York, at the San Antonio Breast Cancer Symposium.
“Looking forward ... we propose to use TMEM doorway density as a prognostic marker for distant recurrence-free survival as a marker of dissemination, and also as a predictive marker of response to drugs that can block TMEM doorways,” she said at a briefing held prior to the presentation of data in an oral abstract session.
Entry points
As their name implies, TMEM doorways are transient entry points or portals that allow cancer cells to disseminate to distant sites. TMEM doorways are composed of tumor cells, macrophages, and endothelial cells that come into direct contact and together create temporary vascular openings that allow tumor cells to cross cell walls into circulation, where they can then hitch a ride and travel to distant organ sites.
Previous studies have shown that TMEM doorway density is a prognostic marker of metastasis in breast cancer patients treated with adjuvant chemotherapy. And as Dr. Oktay and colleagues showed in the current study, TMEM doorway density, as measured by a TMEM doorway score, is a prognostic marker for distant metastatic recurrence of ER+/HER2– breast cancer following neoadjuvant chemotherapy.
They also showed that neoadjuvant chemotherapy may increase the TMEM doorway score and lead to a pro–metastatic tumor microenvironment in some women.
Doorway scores
The investigators measured TMEM doorway scores from residual breast cancers in women who had undergone standard neoadjuvant chemotherapy. The cohort consisted of 96 Black women, 43 of whom had ER+/HER2– breast cancer and 37 of whom had triple-negative breast cancer (TNBC), and 87 White women, 50 with ER+/HER2– cancer and 22 with TNBC. The remaining patients had other breast cancer subtypes.
They found that TNBCs had higher TMEM doorway density score and higher macrophage density scores, which may explain why patients with TNBC often have early recurrence of disease.
They also found that, compared with White patients, Black patients with ER+/HER2– tumors, but not TNBC tumors, had higher TMEM doorway density scores. Similarly, Black patients with ER+/HER– cancers, but not TNBC, had higher macrophage levels than White women, a finding that may explain racial disparity in ER+/HER2– disease, Dr. Oktay said.
For the entire cohort, patients with high TMEM doorway density scores had significantly worse distant recurrence–free survival than patients with intermediate or low scores (P = .008), and there was a trend toward worse DRFS among all patients with ER+/HER2– who were in the highest third of scores, but this did not quite reach statistical significance.
High versus low TMEM doorway density score was also an independent prognostic factor for worse outcomes among the entire cohort (P = .01).
There was no significant difference in TMEM density scores among patients with TNBC.
Neither high macrophage counts nor microvascular density alone were significantly associated with inferior DRFS. TMEM doorway score was the only factor significantly prognostic for worse outcomes among patients in the entire cohort.
Hypothesis needs further testing
Invited discussant Lori Pierce, MD, a radiation oncologist with Michigan Medicine, University of Michigan, Ann Arbor, said it’s unclear whether TMEM doorway density changed following neoadjuvant chemotherapy as there were no prechemotherapy scores available in this study.
“But I think the key part is that, if we think neoadjuvant chemotherapy promotes metastasis, then there should be an inferior outcome compared to adjuvant chemotherapy, but that’s not what we see. Well-powered randomized trials show equivalent outcomes with neoadjuvant chemotherapy as well as adjuvant,” she said.
She noted that a 2018 meta-analysis of individual patient data from 10 randomized trials comparing neoadjuvant with adjuvant chemotherapy in early breast cancer showed no differences in long-term distant recurrences, breast cancer–specific mortality, or all-cause mortality between the two modalities.
“While I think these data are very provocative, I certainly wouldn’t want Black women or any women who need neoadjuvant therapy to be discouraged because of these data. We need these data to be tested rigorously, so I look forward to the clinical trials that will test this question and can really give us more information about this very interesting hypothesis,” Dr. Pierce said.
The study was funded by the National Institutes of Health, New York State Department of Health Peter T. Rowley Breast Cancer Scientific Research Projects, Helen & Irving Spatz Family Foundation, Evelyn Gruss Lipper Charitable Foundation, and the Gruss-Lipper Biophotonics Center and the integrated imaging program at the Albert Einstein College of Medicine. Dr. Oktay reported no conflicts of interests.
SAN ANTONIO – compared with White women, a discovery that may at least partially explain racial differences in breast cancer outcomes, investigators say.
The finding, which comes from a retrospective study comparing differences in tumor microenvironment of metastasis (TMEM) “doorways” between Black and White women suggest that tumors in Black women may have a stronger prometastatic response to neoadjuvant chemotherapy than tumors in White women, reported Maja H. Oktay, MD, PhD, of Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, New York, at the San Antonio Breast Cancer Symposium.
“Looking forward ... we propose to use TMEM doorway density as a prognostic marker for distant recurrence-free survival as a marker of dissemination, and also as a predictive marker of response to drugs that can block TMEM doorways,” she said at a briefing held prior to the presentation of data in an oral abstract session.
Entry points
As their name implies, TMEM doorways are transient entry points or portals that allow cancer cells to disseminate to distant sites. TMEM doorways are composed of tumor cells, macrophages, and endothelial cells that come into direct contact and together create temporary vascular openings that allow tumor cells to cross cell walls into circulation, where they can then hitch a ride and travel to distant organ sites.
Previous studies have shown that TMEM doorway density is a prognostic marker of metastasis in breast cancer patients treated with adjuvant chemotherapy. And as Dr. Oktay and colleagues showed in the current study, TMEM doorway density, as measured by a TMEM doorway score, is a prognostic marker for distant metastatic recurrence of ER+/HER2– breast cancer following neoadjuvant chemotherapy.
They also showed that neoadjuvant chemotherapy may increase the TMEM doorway score and lead to a pro–metastatic tumor microenvironment in some women.
Doorway scores
The investigators measured TMEM doorway scores from residual breast cancers in women who had undergone standard neoadjuvant chemotherapy. The cohort consisted of 96 Black women, 43 of whom had ER+/HER2– breast cancer and 37 of whom had triple-negative breast cancer (TNBC), and 87 White women, 50 with ER+/HER2– cancer and 22 with TNBC. The remaining patients had other breast cancer subtypes.
They found that TNBCs had higher TMEM doorway density score and higher macrophage density scores, which may explain why patients with TNBC often have early recurrence of disease.
They also found that, compared with White patients, Black patients with ER+/HER2– tumors, but not TNBC tumors, had higher TMEM doorway density scores. Similarly, Black patients with ER+/HER– cancers, but not TNBC, had higher macrophage levels than White women, a finding that may explain racial disparity in ER+/HER2– disease, Dr. Oktay said.
For the entire cohort, patients with high TMEM doorway density scores had significantly worse distant recurrence–free survival than patients with intermediate or low scores (P = .008), and there was a trend toward worse DRFS among all patients with ER+/HER2– who were in the highest third of scores, but this did not quite reach statistical significance.
High versus low TMEM doorway density score was also an independent prognostic factor for worse outcomes among the entire cohort (P = .01).
There was no significant difference in TMEM density scores among patients with TNBC.
Neither high macrophage counts nor microvascular density alone were significantly associated with inferior DRFS. TMEM doorway score was the only factor significantly prognostic for worse outcomes among patients in the entire cohort.
Hypothesis needs further testing
Invited discussant Lori Pierce, MD, a radiation oncologist with Michigan Medicine, University of Michigan, Ann Arbor, said it’s unclear whether TMEM doorway density changed following neoadjuvant chemotherapy as there were no prechemotherapy scores available in this study.
“But I think the key part is that, if we think neoadjuvant chemotherapy promotes metastasis, then there should be an inferior outcome compared to adjuvant chemotherapy, but that’s not what we see. Well-powered randomized trials show equivalent outcomes with neoadjuvant chemotherapy as well as adjuvant,” she said.
She noted that a 2018 meta-analysis of individual patient data from 10 randomized trials comparing neoadjuvant with adjuvant chemotherapy in early breast cancer showed no differences in long-term distant recurrences, breast cancer–specific mortality, or all-cause mortality between the two modalities.
“While I think these data are very provocative, I certainly wouldn’t want Black women or any women who need neoadjuvant therapy to be discouraged because of these data. We need these data to be tested rigorously, so I look forward to the clinical trials that will test this question and can really give us more information about this very interesting hypothesis,” Dr. Pierce said.
The study was funded by the National Institutes of Health, New York State Department of Health Peter T. Rowley Breast Cancer Scientific Research Projects, Helen & Irving Spatz Family Foundation, Evelyn Gruss Lipper Charitable Foundation, and the Gruss-Lipper Biophotonics Center and the integrated imaging program at the Albert Einstein College of Medicine. Dr. Oktay reported no conflicts of interests.
AT SABCS 2022
Less than a third of Americans aware of cancer risk from alcohol
The new findings, from a nationally representative survey that included responses from 3,865 adults, show a low awareness of the cancer risk from alcohol, and also that the risk varies by type of drink. Just under a third (31.2%) of respondents thought that consuming liquor/spirits was associated with a risk of cancer, but this fell to 24.9% for drinking beer and even further, to 20.3%, for drinking wine.
In fact, some respondents though the opposite – that drinking alcohol has health benefits; 10.3% of respondents thought that drinking wine was associated with a decreased cancer risk, while 2.25% thought the same for drinking beer, and 1.7% thought that for drinking liquor.
Most U.S. adults (> 50%) reported not knowing how these beverages affected cancer risk, the authors report.
“This study’s findings underscore the need to develop interventions for educating the public about the cancer risks of alcohol use, particularly in the prevailing context of national dialogue about the purported heart health benefits of wine,” commented senior author William M. P. Klein, PhD, associate director of the National Cancer Institute’s Behavioral Research Program, in a statement.
“All types of alcoholic beverages, including wine, increase cancer risk,” Dr. Klein said.
The findings were published online in Cancer Epidemiology, Biomarkers & Prevention.
The results echo the findings of a previous national survey that also found that the majority of Americans are not aware that alcohol consumption is associated with an increased risk of developing a variety of cancers.
In contrast, within the scientific community, there is long-standing and increasing awareness of alcohol consumption as a leading modifiable risk factor for cancer, and there is a growing movement calling for more public health awareness of the link.
Recently, there has been some public support for adding written warnings about the cancer risk from alcohol. A Citizen Petition was filed in 2021, and in August 2022, The New England Journal of Medicine issued a call for new labeling.
Several cancer organizations are petitioning for warnings to be added to alcoholic beverages. The petition is supported by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations. Proposed labeling would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Dr. Klein and colleagues suggest that public health interventions, including mass media campaigns, cancer warning labels, and patient-provider communications, could help disseminate information about cancer and alcohol. “Educating the public about how alcohol increases cancer risk will not only empower consumers to make more informed decisions but may also prevent and reduce excessive alcohol use, as well as cancer morbidity and mortality,” Dr. Klein said.
The study was supported by the Division of Cancer Control and Population Sciences at the National Cancer Institute. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The new findings, from a nationally representative survey that included responses from 3,865 adults, show a low awareness of the cancer risk from alcohol, and also that the risk varies by type of drink. Just under a third (31.2%) of respondents thought that consuming liquor/spirits was associated with a risk of cancer, but this fell to 24.9% for drinking beer and even further, to 20.3%, for drinking wine.
In fact, some respondents though the opposite – that drinking alcohol has health benefits; 10.3% of respondents thought that drinking wine was associated with a decreased cancer risk, while 2.25% thought the same for drinking beer, and 1.7% thought that for drinking liquor.
Most U.S. adults (> 50%) reported not knowing how these beverages affected cancer risk, the authors report.
“This study’s findings underscore the need to develop interventions for educating the public about the cancer risks of alcohol use, particularly in the prevailing context of national dialogue about the purported heart health benefits of wine,” commented senior author William M. P. Klein, PhD, associate director of the National Cancer Institute’s Behavioral Research Program, in a statement.
“All types of alcoholic beverages, including wine, increase cancer risk,” Dr. Klein said.
The findings were published online in Cancer Epidemiology, Biomarkers & Prevention.
The results echo the findings of a previous national survey that also found that the majority of Americans are not aware that alcohol consumption is associated with an increased risk of developing a variety of cancers.
In contrast, within the scientific community, there is long-standing and increasing awareness of alcohol consumption as a leading modifiable risk factor for cancer, and there is a growing movement calling for more public health awareness of the link.
Recently, there has been some public support for adding written warnings about the cancer risk from alcohol. A Citizen Petition was filed in 2021, and in August 2022, The New England Journal of Medicine issued a call for new labeling.
Several cancer organizations are petitioning for warnings to be added to alcoholic beverages. The petition is supported by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations. Proposed labeling would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Dr. Klein and colleagues suggest that public health interventions, including mass media campaigns, cancer warning labels, and patient-provider communications, could help disseminate information about cancer and alcohol. “Educating the public about how alcohol increases cancer risk will not only empower consumers to make more informed decisions but may also prevent and reduce excessive alcohol use, as well as cancer morbidity and mortality,” Dr. Klein said.
The study was supported by the Division of Cancer Control and Population Sciences at the National Cancer Institute. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The new findings, from a nationally representative survey that included responses from 3,865 adults, show a low awareness of the cancer risk from alcohol, and also that the risk varies by type of drink. Just under a third (31.2%) of respondents thought that consuming liquor/spirits was associated with a risk of cancer, but this fell to 24.9% for drinking beer and even further, to 20.3%, for drinking wine.
In fact, some respondents though the opposite – that drinking alcohol has health benefits; 10.3% of respondents thought that drinking wine was associated with a decreased cancer risk, while 2.25% thought the same for drinking beer, and 1.7% thought that for drinking liquor.
Most U.S. adults (> 50%) reported not knowing how these beverages affected cancer risk, the authors report.
“This study’s findings underscore the need to develop interventions for educating the public about the cancer risks of alcohol use, particularly in the prevailing context of national dialogue about the purported heart health benefits of wine,” commented senior author William M. P. Klein, PhD, associate director of the National Cancer Institute’s Behavioral Research Program, in a statement.
“All types of alcoholic beverages, including wine, increase cancer risk,” Dr. Klein said.
The findings were published online in Cancer Epidemiology, Biomarkers & Prevention.
The results echo the findings of a previous national survey that also found that the majority of Americans are not aware that alcohol consumption is associated with an increased risk of developing a variety of cancers.
In contrast, within the scientific community, there is long-standing and increasing awareness of alcohol consumption as a leading modifiable risk factor for cancer, and there is a growing movement calling for more public health awareness of the link.
Recently, there has been some public support for adding written warnings about the cancer risk from alcohol. A Citizen Petition was filed in 2021, and in August 2022, The New England Journal of Medicine issued a call for new labeling.
Several cancer organizations are petitioning for warnings to be added to alcoholic beverages. The petition is supported by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations. Proposed labeling would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Dr. Klein and colleagues suggest that public health interventions, including mass media campaigns, cancer warning labels, and patient-provider communications, could help disseminate information about cancer and alcohol. “Educating the public about how alcohol increases cancer risk will not only empower consumers to make more informed decisions but may also prevent and reduce excessive alcohol use, as well as cancer morbidity and mortality,” Dr. Klein said.
The study was supported by the Division of Cancer Control and Population Sciences at the National Cancer Institute. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANCER EPIDEMIOLOGY, BIOMARKERS & PREVENTION
Deductibles a threat to more imaging after abnormal mammogram
CHICAGO – One in five women will skip further imaging after an abnormal mammogram if they have to pay out of pocket before their deductible is met, new data indicate.
“The ACA [Affordable Care Act] removed out-of-pocket costs for screening mammograms under most health plans to encourage women to partake in this important preventative health care measure,” Michael Ngo, MD, a radiology resident at Boston Medical Center and Boston University, said in a statement.
However, the screening mammogram is only the first step. If it’s abnormal, additional tests and a biopsy help determine whether the patient has cancer. The ACA does not mandate coverage for those, Dr. Ngo noted.
Dr. Ngo was lead author of the study presented at the annual meeting of the Radiological Society of North America.
Researchers collected 932 surveys. Asked whether they would skip follow-up imaging if they knew that they would have to pay a deductible, 151 of 714 (21.2%) said that they would skip the imaging; 424 (59.4%) said that they would not skip further imaging; and 139 (19.5%) were undecided. Responses differed by race, education level, household income, and insurance payer.
Groups most likely to forgo further tests
The groups with the highest percentage of persons who would skip additional imaging were Hispanic persons (33%); persons whose level of education was high school or less (31.0%); persons with a household income of less than $35,000 (27%); and those covered by Medicaid or who were uninsured (31.5%).
Wendie Berg, MD, PhD, professor of radiology at the University of Pittsburgh, who was not part of the study, said that because insurance companies had to cover initial mammograms fully under the ACA, “they generally increased deductibles. That resulted in more charges to patients when they came in for additional testing.
“It caught a lot of women by surprise,” she told this news organization.
The out-of-pocket charges can escalate with each step – more images, a biopsy, then more if they do have cancer, she said. This puts patients on the hook for hundreds, if not thousands, of dollars in medical bills.
However, Dr. Berg said, “The vast majority of women – 95% – who are called back for additional testing don’t have cancer. It is a problem that a lot of women will experience the cost and don’t have any benefit.”
Reducing false-positive recalls
The study highlights several things, she said. One is that “it’s incumbent on all of us to reduce false-positive recalls, which is one of the benefits of 3-D mammogram.”
Physicians who order additional tests must also consider the financial burden for patients, she said.
Some states have tackled the issue, she said. “Seven states do require insurance to cover diagnostic testing.” But those states differ in the extent of the coverage. DenseBreast-info.org, a website she helps with on a volunteer basis, explains the benefits by state.
Further compounding the problem is that not every insurer is subject to state law, she said.
Many states have programs that cover the cost for those who meet income requirements, although, she noted, some women make too much to qualify.
“It would be great to have a federal law that is inclusive,” she said.
Education efforts may help
Brian N. Dontchos, MD, with the University of Washington in Seattle, who was not part of the study, views the data another way. He told this news organization, “It is encouraging from the study that the majority of women would pursue additional imaging after an abnormal screening mammogram despite incurring more cost.”
He said that since direct patient education “has been shown to be effective in improving patient participation in screening programs, it is possible that, with more education of patients and providers, that advocacy could influence payers to support downstream imaging and biopsies that result from screening programs.”
Dr. Ngo, Dr. Berg, and Dr. Dontchos report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – One in five women will skip further imaging after an abnormal mammogram if they have to pay out of pocket before their deductible is met, new data indicate.
“The ACA [Affordable Care Act] removed out-of-pocket costs for screening mammograms under most health plans to encourage women to partake in this important preventative health care measure,” Michael Ngo, MD, a radiology resident at Boston Medical Center and Boston University, said in a statement.
However, the screening mammogram is only the first step. If it’s abnormal, additional tests and a biopsy help determine whether the patient has cancer. The ACA does not mandate coverage for those, Dr. Ngo noted.
Dr. Ngo was lead author of the study presented at the annual meeting of the Radiological Society of North America.
Researchers collected 932 surveys. Asked whether they would skip follow-up imaging if they knew that they would have to pay a deductible, 151 of 714 (21.2%) said that they would skip the imaging; 424 (59.4%) said that they would not skip further imaging; and 139 (19.5%) were undecided. Responses differed by race, education level, household income, and insurance payer.
Groups most likely to forgo further tests
The groups with the highest percentage of persons who would skip additional imaging were Hispanic persons (33%); persons whose level of education was high school or less (31.0%); persons with a household income of less than $35,000 (27%); and those covered by Medicaid or who were uninsured (31.5%).
Wendie Berg, MD, PhD, professor of radiology at the University of Pittsburgh, who was not part of the study, said that because insurance companies had to cover initial mammograms fully under the ACA, “they generally increased deductibles. That resulted in more charges to patients when they came in for additional testing.
“It caught a lot of women by surprise,” she told this news organization.
The out-of-pocket charges can escalate with each step – more images, a biopsy, then more if they do have cancer, she said. This puts patients on the hook for hundreds, if not thousands, of dollars in medical bills.
However, Dr. Berg said, “The vast majority of women – 95% – who are called back for additional testing don’t have cancer. It is a problem that a lot of women will experience the cost and don’t have any benefit.”
Reducing false-positive recalls
The study highlights several things, she said. One is that “it’s incumbent on all of us to reduce false-positive recalls, which is one of the benefits of 3-D mammogram.”
Physicians who order additional tests must also consider the financial burden for patients, she said.
Some states have tackled the issue, she said. “Seven states do require insurance to cover diagnostic testing.” But those states differ in the extent of the coverage. DenseBreast-info.org, a website she helps with on a volunteer basis, explains the benefits by state.
Further compounding the problem is that not every insurer is subject to state law, she said.
Many states have programs that cover the cost for those who meet income requirements, although, she noted, some women make too much to qualify.
“It would be great to have a federal law that is inclusive,” she said.
Education efforts may help
Brian N. Dontchos, MD, with the University of Washington in Seattle, who was not part of the study, views the data another way. He told this news organization, “It is encouraging from the study that the majority of women would pursue additional imaging after an abnormal screening mammogram despite incurring more cost.”
He said that since direct patient education “has been shown to be effective in improving patient participation in screening programs, it is possible that, with more education of patients and providers, that advocacy could influence payers to support downstream imaging and biopsies that result from screening programs.”
Dr. Ngo, Dr. Berg, and Dr. Dontchos report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – One in five women will skip further imaging after an abnormal mammogram if they have to pay out of pocket before their deductible is met, new data indicate.
“The ACA [Affordable Care Act] removed out-of-pocket costs for screening mammograms under most health plans to encourage women to partake in this important preventative health care measure,” Michael Ngo, MD, a radiology resident at Boston Medical Center and Boston University, said in a statement.
However, the screening mammogram is only the first step. If it’s abnormal, additional tests and a biopsy help determine whether the patient has cancer. The ACA does not mandate coverage for those, Dr. Ngo noted.
Dr. Ngo was lead author of the study presented at the annual meeting of the Radiological Society of North America.
Researchers collected 932 surveys. Asked whether they would skip follow-up imaging if they knew that they would have to pay a deductible, 151 of 714 (21.2%) said that they would skip the imaging; 424 (59.4%) said that they would not skip further imaging; and 139 (19.5%) were undecided. Responses differed by race, education level, household income, and insurance payer.
Groups most likely to forgo further tests
The groups with the highest percentage of persons who would skip additional imaging were Hispanic persons (33%); persons whose level of education was high school or less (31.0%); persons with a household income of less than $35,000 (27%); and those covered by Medicaid or who were uninsured (31.5%).
Wendie Berg, MD, PhD, professor of radiology at the University of Pittsburgh, who was not part of the study, said that because insurance companies had to cover initial mammograms fully under the ACA, “they generally increased deductibles. That resulted in more charges to patients when they came in for additional testing.
“It caught a lot of women by surprise,” she told this news organization.
The out-of-pocket charges can escalate with each step – more images, a biopsy, then more if they do have cancer, she said. This puts patients on the hook for hundreds, if not thousands, of dollars in medical bills.
However, Dr. Berg said, “The vast majority of women – 95% – who are called back for additional testing don’t have cancer. It is a problem that a lot of women will experience the cost and don’t have any benefit.”
Reducing false-positive recalls
The study highlights several things, she said. One is that “it’s incumbent on all of us to reduce false-positive recalls, which is one of the benefits of 3-D mammogram.”
Physicians who order additional tests must also consider the financial burden for patients, she said.
Some states have tackled the issue, she said. “Seven states do require insurance to cover diagnostic testing.” But those states differ in the extent of the coverage. DenseBreast-info.org, a website she helps with on a volunteer basis, explains the benefits by state.
Further compounding the problem is that not every insurer is subject to state law, she said.
Many states have programs that cover the cost for those who meet income requirements, although, she noted, some women make too much to qualify.
“It would be great to have a federal law that is inclusive,” she said.
Education efforts may help
Brian N. Dontchos, MD, with the University of Washington in Seattle, who was not part of the study, views the data another way. He told this news organization, “It is encouraging from the study that the majority of women would pursue additional imaging after an abnormal screening mammogram despite incurring more cost.”
He said that since direct patient education “has been shown to be effective in improving patient participation in screening programs, it is possible that, with more education of patients and providers, that advocacy could influence payers to support downstream imaging and biopsies that result from screening programs.”
Dr. Ngo, Dr. Berg, and Dr. Dontchos report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT RSNA 2022
Managing trastuzumab deruxtecan adverse events in the real world
With recent expansions in its breast cancer indications, there has been an increase in the use of trastuzumab deruxtecan (T-DXd; Enhertu).
“A lot of us are using this more frequently now than we were in the past,” explained Sid Yadav, MD, a breast and gynecologic cancer specialist at the Mayo Clinic in Rochester, Minn. However, he added that managing its adverse events has been a “bit of a learning curve for all of us.”
The antibody-drug conjugate has been on the market since 2019 for metastatic human epidermal growth factor receptor (HER2)–positive breast cancer, but it was then approved in May 2022 for earlier use in this patient population and in August 2022 for patients with HER2-low disease. This latest approval was based on data showing an improvement in overall survival that was described as “practice changing.”
In addition, T-DXd is also approved for use in metastatic HER2-mutated non–small cell lung cancer and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma.
, Dr. Yadav told this news organization.
Among the eight or so patients he’s seen or treated over 2 months, Dr. Yadav has already seen one case of high-grade interstitial lung disease/pneumonitis, a complication that “everybody worries about” because the label for T-DXd carries a black box warning of this possibility.
There have been other issues at Mayo Clinic, as well. In one recent week, five patients were admitted for possible T-DXd adverse events, including neutropenic fever and sepsis; pneumonitis; severe nausea/vomiting with electrolyte imbalance; pneumonia, and non–ST elevation myocardial infarction with low ejection fraction.
It’s unknown what proportion of T-DXd recipients the five admissions represented. Dr. Yadav’s service has over 10 breast oncologists, so the cases could represent maybe 1%-10% of patients, he said.
His experience prompted Dr. Yadav to turn to Twitter to ask fellow oncologists what complications they’ve seen with T-DXd.
One said that his “real-world toxicity experience [has been] worse than the trial data,” which isn’t unusual, another oncologist noted, because real-world patients are often sicker than trial participants and more vulnerable to toxicities.
A third oncologist countered that she has “found [T-DXd] generally easy for patients to tolerate and [has] not needed to admit anyone” so far.
Overall, Dr. Yadav said that in his experience there are issues that need to be considered with T-DXd beyond interstitial lung disease.
As with any chemotherapy, neutropenia and infections are a concern, as the labeling notes. The interstitial lung disease case has also made Dr. Yadav have a low threshold to order CT in patients with any hints of shortness of breath and to start steroids if there’s any suspicion.
Probably the most common issue, however, is nausea and vomiting. In clinical trials, over 70% of participants reported nausea and over 40% experienced vomiting.
In response, Dr. Yadav and his colleagues have become more aggressive with prophylaxis. Pretreatment includes steroids, palonosetron, and fosaprepitant. Patients are also usually sent home with prochlorperazine, ondansetron, and lorazepam. If these don’t help, the team considers olanzapine.
They have also learned that “it’s important to spend that extra 15-20 minutes upfront” with patients before starting T-DXd to explain the risk for nausea and vomiting and how it will be managed, Dr. Yadav commented. “We do chemotherapy teaching for every patient, but I think we spend more time [now] talking about nausea and vomiting with this subset,” he said.
Dr. Yadav still starts patients on the standard breast cancer dose of T-DXd – 5.4 mg/kg every 3 weeks – but said he’s quicker now to lower the dose if patients aren’t doing well. He estimates he’s done that a couple of times so far.
Approaches at the Mayo Clinic are in line with those in a recent article on managing T-DXd toxicities by Hope Rugo, MD, from the University of California, San Francisco, and colleagues.
These authors conclude that adverse events related to T-DXd are frequent but are most commonly low grade and manageable. Nausea and vomiting are among the most common, and they note that interstitial lung disease/pneumonitis is an important adverse event, for which proactive monitoring, diagnosis, and management are key.
The review describes management practices of other health care providers and institutions with experience in using T-DXd to help with safe and effective management of the drug’s adverse events, particularly since the duration of treatment may be quite long.
Proper management of T-DXd–related adverse events will allow optimal exposure to and benefit from the drug and will help avoid premature discontinuation or improper dose reductions, Dr. Rugo and colleagues commented.
Dr. Yadav reports no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
With recent expansions in its breast cancer indications, there has been an increase in the use of trastuzumab deruxtecan (T-DXd; Enhertu).
“A lot of us are using this more frequently now than we were in the past,” explained Sid Yadav, MD, a breast and gynecologic cancer specialist at the Mayo Clinic in Rochester, Minn. However, he added that managing its adverse events has been a “bit of a learning curve for all of us.”
The antibody-drug conjugate has been on the market since 2019 for metastatic human epidermal growth factor receptor (HER2)–positive breast cancer, but it was then approved in May 2022 for earlier use in this patient population and in August 2022 for patients with HER2-low disease. This latest approval was based on data showing an improvement in overall survival that was described as “practice changing.”
In addition, T-DXd is also approved for use in metastatic HER2-mutated non–small cell lung cancer and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma.
, Dr. Yadav told this news organization.
Among the eight or so patients he’s seen or treated over 2 months, Dr. Yadav has already seen one case of high-grade interstitial lung disease/pneumonitis, a complication that “everybody worries about” because the label for T-DXd carries a black box warning of this possibility.
There have been other issues at Mayo Clinic, as well. In one recent week, five patients were admitted for possible T-DXd adverse events, including neutropenic fever and sepsis; pneumonitis; severe nausea/vomiting with electrolyte imbalance; pneumonia, and non–ST elevation myocardial infarction with low ejection fraction.
It’s unknown what proportion of T-DXd recipients the five admissions represented. Dr. Yadav’s service has over 10 breast oncologists, so the cases could represent maybe 1%-10% of patients, he said.
His experience prompted Dr. Yadav to turn to Twitter to ask fellow oncologists what complications they’ve seen with T-DXd.
One said that his “real-world toxicity experience [has been] worse than the trial data,” which isn’t unusual, another oncologist noted, because real-world patients are often sicker than trial participants and more vulnerable to toxicities.
A third oncologist countered that she has “found [T-DXd] generally easy for patients to tolerate and [has] not needed to admit anyone” so far.
Overall, Dr. Yadav said that in his experience there are issues that need to be considered with T-DXd beyond interstitial lung disease.
As with any chemotherapy, neutropenia and infections are a concern, as the labeling notes. The interstitial lung disease case has also made Dr. Yadav have a low threshold to order CT in patients with any hints of shortness of breath and to start steroids if there’s any suspicion.
Probably the most common issue, however, is nausea and vomiting. In clinical trials, over 70% of participants reported nausea and over 40% experienced vomiting.
In response, Dr. Yadav and his colleagues have become more aggressive with prophylaxis. Pretreatment includes steroids, palonosetron, and fosaprepitant. Patients are also usually sent home with prochlorperazine, ondansetron, and lorazepam. If these don’t help, the team considers olanzapine.
They have also learned that “it’s important to spend that extra 15-20 minutes upfront” with patients before starting T-DXd to explain the risk for nausea and vomiting and how it will be managed, Dr. Yadav commented. “We do chemotherapy teaching for every patient, but I think we spend more time [now] talking about nausea and vomiting with this subset,” he said.
Dr. Yadav still starts patients on the standard breast cancer dose of T-DXd – 5.4 mg/kg every 3 weeks – but said he’s quicker now to lower the dose if patients aren’t doing well. He estimates he’s done that a couple of times so far.
Approaches at the Mayo Clinic are in line with those in a recent article on managing T-DXd toxicities by Hope Rugo, MD, from the University of California, San Francisco, and colleagues.
These authors conclude that adverse events related to T-DXd are frequent but are most commonly low grade and manageable. Nausea and vomiting are among the most common, and they note that interstitial lung disease/pneumonitis is an important adverse event, for which proactive monitoring, diagnosis, and management are key.
The review describes management practices of other health care providers and institutions with experience in using T-DXd to help with safe and effective management of the drug’s adverse events, particularly since the duration of treatment may be quite long.
Proper management of T-DXd–related adverse events will allow optimal exposure to and benefit from the drug and will help avoid premature discontinuation or improper dose reductions, Dr. Rugo and colleagues commented.
Dr. Yadav reports no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
With recent expansions in its breast cancer indications, there has been an increase in the use of trastuzumab deruxtecan (T-DXd; Enhertu).
“A lot of us are using this more frequently now than we were in the past,” explained Sid Yadav, MD, a breast and gynecologic cancer specialist at the Mayo Clinic in Rochester, Minn. However, he added that managing its adverse events has been a “bit of a learning curve for all of us.”
The antibody-drug conjugate has been on the market since 2019 for metastatic human epidermal growth factor receptor (HER2)–positive breast cancer, but it was then approved in May 2022 for earlier use in this patient population and in August 2022 for patients with HER2-low disease. This latest approval was based on data showing an improvement in overall survival that was described as “practice changing.”
In addition, T-DXd is also approved for use in metastatic HER2-mutated non–small cell lung cancer and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma.
, Dr. Yadav told this news organization.
Among the eight or so patients he’s seen or treated over 2 months, Dr. Yadav has already seen one case of high-grade interstitial lung disease/pneumonitis, a complication that “everybody worries about” because the label for T-DXd carries a black box warning of this possibility.
There have been other issues at Mayo Clinic, as well. In one recent week, five patients were admitted for possible T-DXd adverse events, including neutropenic fever and sepsis; pneumonitis; severe nausea/vomiting with electrolyte imbalance; pneumonia, and non–ST elevation myocardial infarction with low ejection fraction.
It’s unknown what proportion of T-DXd recipients the five admissions represented. Dr. Yadav’s service has over 10 breast oncologists, so the cases could represent maybe 1%-10% of patients, he said.
His experience prompted Dr. Yadav to turn to Twitter to ask fellow oncologists what complications they’ve seen with T-DXd.
One said that his “real-world toxicity experience [has been] worse than the trial data,” which isn’t unusual, another oncologist noted, because real-world patients are often sicker than trial participants and more vulnerable to toxicities.
A third oncologist countered that she has “found [T-DXd] generally easy for patients to tolerate and [has] not needed to admit anyone” so far.
Overall, Dr. Yadav said that in his experience there are issues that need to be considered with T-DXd beyond interstitial lung disease.
As with any chemotherapy, neutropenia and infections are a concern, as the labeling notes. The interstitial lung disease case has also made Dr. Yadav have a low threshold to order CT in patients with any hints of shortness of breath and to start steroids if there’s any suspicion.
Probably the most common issue, however, is nausea and vomiting. In clinical trials, over 70% of participants reported nausea and over 40% experienced vomiting.
In response, Dr. Yadav and his colleagues have become more aggressive with prophylaxis. Pretreatment includes steroids, palonosetron, and fosaprepitant. Patients are also usually sent home with prochlorperazine, ondansetron, and lorazepam. If these don’t help, the team considers olanzapine.
They have also learned that “it’s important to spend that extra 15-20 minutes upfront” with patients before starting T-DXd to explain the risk for nausea and vomiting and how it will be managed, Dr. Yadav commented. “We do chemotherapy teaching for every patient, but I think we spend more time [now] talking about nausea and vomiting with this subset,” he said.
Dr. Yadav still starts patients on the standard breast cancer dose of T-DXd – 5.4 mg/kg every 3 weeks – but said he’s quicker now to lower the dose if patients aren’t doing well. He estimates he’s done that a couple of times so far.
Approaches at the Mayo Clinic are in line with those in a recent article on managing T-DXd toxicities by Hope Rugo, MD, from the University of California, San Francisco, and colleagues.
These authors conclude that adverse events related to T-DXd are frequent but are most commonly low grade and manageable. Nausea and vomiting are among the most common, and they note that interstitial lung disease/pneumonitis is an important adverse event, for which proactive monitoring, diagnosis, and management are key.
The review describes management practices of other health care providers and institutions with experience in using T-DXd to help with safe and effective management of the drug’s adverse events, particularly since the duration of treatment may be quite long.
Proper management of T-DXd–related adverse events will allow optimal exposure to and benefit from the drug and will help avoid premature discontinuation or improper dose reductions, Dr. Rugo and colleagues commented.
Dr. Yadav reports no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Whole breast radiation for breast cancer shown to be safe and effective
The findings from a phase 3 clinical trial are a boon to patient convenience.
“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.
“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.
The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.
“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.
Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.
The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.
Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).
“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.
The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.
The findings from a phase 3 clinical trial are a boon to patient convenience.
“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.
“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.
The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.
“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.
Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.
The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.
Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).
“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.
The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.
The findings from a phase 3 clinical trial are a boon to patient convenience.
“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.
“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.
The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.
“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.
Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.
The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.
Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).
“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.
The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.
FROM ASTRO 2022
Commentary: New treatments and management in breast cancer, December 2022
Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.3
Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.4
Additional References
- Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
- Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
- Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
- Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015
Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.3
Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.4
Additional References
- Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
- Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
- Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
- Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015
Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.3
Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.4
Additional References
- Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
- Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
- Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
- Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015
HER2+ BC: Crofelemer fails to prevent any grade chemotherapy-induced diarrhea in phase 2
Key clinical point: Crofelemer failed to reduce the incidence rate of any grade chemotherapy-induced diarrhea (CID) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) who received trastuzumab, pertuzumab, and a taxane.
Major finding: During cycle 2 of chemotherapy, a similar proportion of patients reported any grade diarrhea for ≥2 consecutive days (P = .742), but the rate of grade ≥2 diarrhea was significantly reduced (8.0% vs 39.1%; P = .0196) in the crofelemer vs no scheduled prophylactic medication treatment group.
Study details: Findings are from the phase 2 HALT-D study including 51 patients with HER2+ BC who were randomly assigned to receive 125 mg crofelemer or no scheduled prophylactic medication during cycles 1 and 2 of chemotherapy/HER2-targeted therapy.
Disclosures: This study was supported by Genentech, Inc., and other sources. The authors declared serving as consultants, advisors or receiving honoraria, research funding, consulting fees, speaking fees, or travel support from several sources, including Genentech.
Source: Pohlmann PR et al. HALT-D: A randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane. Breast Cancer Res Treat. 2022;196(3):571-581 (Oct 25). Doi: 10.1007/s10549-022-06743-9
Key clinical point: Crofelemer failed to reduce the incidence rate of any grade chemotherapy-induced diarrhea (CID) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) who received trastuzumab, pertuzumab, and a taxane.
Major finding: During cycle 2 of chemotherapy, a similar proportion of patients reported any grade diarrhea for ≥2 consecutive days (P = .742), but the rate of grade ≥2 diarrhea was significantly reduced (8.0% vs 39.1%; P = .0196) in the crofelemer vs no scheduled prophylactic medication treatment group.
Study details: Findings are from the phase 2 HALT-D study including 51 patients with HER2+ BC who were randomly assigned to receive 125 mg crofelemer or no scheduled prophylactic medication during cycles 1 and 2 of chemotherapy/HER2-targeted therapy.
Disclosures: This study was supported by Genentech, Inc., and other sources. The authors declared serving as consultants, advisors or receiving honoraria, research funding, consulting fees, speaking fees, or travel support from several sources, including Genentech.
Source: Pohlmann PR et al. HALT-D: A randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane. Breast Cancer Res Treat. 2022;196(3):571-581 (Oct 25). Doi: 10.1007/s10549-022-06743-9
Key clinical point: Crofelemer failed to reduce the incidence rate of any grade chemotherapy-induced diarrhea (CID) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) who received trastuzumab, pertuzumab, and a taxane.
Major finding: During cycle 2 of chemotherapy, a similar proportion of patients reported any grade diarrhea for ≥2 consecutive days (P = .742), but the rate of grade ≥2 diarrhea was significantly reduced (8.0% vs 39.1%; P = .0196) in the crofelemer vs no scheduled prophylactic medication treatment group.
Study details: Findings are from the phase 2 HALT-D study including 51 patients with HER2+ BC who were randomly assigned to receive 125 mg crofelemer or no scheduled prophylactic medication during cycles 1 and 2 of chemotherapy/HER2-targeted therapy.
Disclosures: This study was supported by Genentech, Inc., and other sources. The authors declared serving as consultants, advisors or receiving honoraria, research funding, consulting fees, speaking fees, or travel support from several sources, including Genentech.
Source: Pohlmann PR et al. HALT-D: A randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane. Breast Cancer Res Treat. 2022;196(3):571-581 (Oct 25). Doi: 10.1007/s10549-022-06743-9
ER+ BC: Elderly patients can opt for endocrine monotherapy and avoid local invasive treatment
Key clinical point: In elderly patients who received endocrine monotherapy for breast cancer (BC), the risk of dying due to other conditions was more than twice the risk for eventually requiring invasive local treatment.
Major finding: Within 5 years, 28% of patients required invasive local treatment (surgery or radiotherapy) and the overall mortality risk (overall survival 42%) was >2 times higher than the risk of undergoing invasive local treatment.
Study details: Findings are from a retrospective cohort study including 91 elderly (≥70 years) female patients with estrogen receptor-positive (ER+) BC who received endocrine monotherapy as a definitive treatment.
Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.
Source: Gooijer SA et al. Long-term outcome of sustained endocrine monotherapy for elderly breast cancer patients. Ann Surg Oncol. 2022 (Nov 3). Doi: 10.1245/s10434-022-12662-2
Key clinical point: In elderly patients who received endocrine monotherapy for breast cancer (BC), the risk of dying due to other conditions was more than twice the risk for eventually requiring invasive local treatment.
Major finding: Within 5 years, 28% of patients required invasive local treatment (surgery or radiotherapy) and the overall mortality risk (overall survival 42%) was >2 times higher than the risk of undergoing invasive local treatment.
Study details: Findings are from a retrospective cohort study including 91 elderly (≥70 years) female patients with estrogen receptor-positive (ER+) BC who received endocrine monotherapy as a definitive treatment.
Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.
Source: Gooijer SA et al. Long-term outcome of sustained endocrine monotherapy for elderly breast cancer patients. Ann Surg Oncol. 2022 (Nov 3). Doi: 10.1245/s10434-022-12662-2
Key clinical point: In elderly patients who received endocrine monotherapy for breast cancer (BC), the risk of dying due to other conditions was more than twice the risk for eventually requiring invasive local treatment.
Major finding: Within 5 years, 28% of patients required invasive local treatment (surgery or radiotherapy) and the overall mortality risk (overall survival 42%) was >2 times higher than the risk of undergoing invasive local treatment.
Study details: Findings are from a retrospective cohort study including 91 elderly (≥70 years) female patients with estrogen receptor-positive (ER+) BC who received endocrine monotherapy as a definitive treatment.
Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.
Source: Gooijer SA et al. Long-term outcome of sustained endocrine monotherapy for elderly breast cancer patients. Ann Surg Oncol. 2022 (Nov 3). Doi: 10.1245/s10434-022-12662-2