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HDAC/aromatase inhibitor combo shows promise for HR+/HER2- advanced breast cancer
MUNICH – For patients with HR-positive (HR+) and human epidermal growth factor receptor 2 (HER2)–advanced breast cancer who have progressed after endocrine therapy, a combination of the oral histone deacetylase (HDAC) inhibitor chidamide and exemestane appears safe and more effective than exemestane alone, according to results from the phase 3 ACE trial.
“This is the first phase 3 trial to demonstrate that an HDAC inhibitor plus endocrine blockade improves progression-free survival, compared to endocrine blockade alone in hormone receptor positive advanced breast cancer patients who have progressed after prior endocrine therapy,” said lead author, Zefei Jiang, MD, at the European Society for Medical Oncology Congress.
HDAC inhibitors have historically been used for psychiatric and neurologic applications, but interest in their antineoplastic potential has increased over the past decade. Chidamide is approved for T-cell lymphoma in China, but not in the United States, where three other HDAC inhibitors are labeled for T-cell lymphoma, and a fourth is approved for multiple myeloma.
Although no HDAC inhibitors are clinically available for breast cancer, the future may tell a different story. The HDAC inhibitor entinostat received a breakthrough therapy designation by the Food and Drug Administration after the phase 2 ENCORE 301 trial showed clinical benefit (also with exemestane for advanced breast cancer). Ongoing studies are also evaluating the potential for HDAC inhibitors in combination with immunotherapy.
“Histone modulation by HDACs is a very important mechanism for epigenetic regulation,” said Dr. Jiang, of the 307th Hospital of Chinese People’s Liberation Army in Beijing, highlighting associations with breast cancer drug resistance. HDAC inhibition may be able to overcome this obstacle by resensitizing tumors to estrogen modulator therapy.
ACE was a double-blind, placebo-controlled study involving 362 patients with HR+/HER2–advanced breast cancer who failed endocrine therapy. Patients had previously received no more than one round of chemotherapy for advanced disease, and no more than four therapies total. The treatment group received either chidamide 30 mg twice weekly with exemestane 25 mg daily (n = 241) or exemestane with placebo (n = 121). Tumor assessments were performed every 8 weeks, and the primary endpoint was progression-free survival (PFS).
The addition of chidamide nearly doubled PFS (7.4 months vs. 3.8 months) and provided a hazard ratio of .75 (P = .0336). Objective response and clinical benefit rates also were increased. At the time of presentation, data were too immature for an overall survival rate.
The most common grade 3 or higher adverse events were hematologic: neutropenia (50.8%), thrombocytopenia (27.5%), and leukopenia (18.8%), all considerably higher than 2.5% for each in the placebo group.
These tolerability issues were expected, however, based on previous chidamide findings.
“Not surprisingly ... 33% of patients had their dose reduced, 50% their dose interrupted, and this is despite the biweekly schedule,” said invited discussant Rebecca Dent, MD, of the National Cancer Centre in Singapore. Despite these issues, Dr. Dent concluded that chidamide otherwise “appears to be quite well tolerated,” and showed meaningful results.
“We now have a second trial demonstrating ... clinical benefit from the addition of HDAC inhibitors to endocrine therapy in [HR+] advanced breast cancer,” Dr. Dent said. “HDAC inhibitors clearly warrant further investigation in earlier settings of [HR+] advanced breast cancer and ... yet to be defined ... subgroups, and obviously we anxiously await the phase 3 results of entinostat.”
In consideration of the future, Dr. Dent suggested that more studies are needed to develop subgroup-targeted therapies and optimize sequencing. “We’ve really underestimated the selective pressure of these treatments and how they impact our subsequent therapies,” she said.
Dr. Dent noted how these factors limit predictive relevance of study findings in clinical practice, in which patients with different treatment histories may have completely different responses to the same agent.
To overcome these obstacles, Dr. Dent encouraged development of biomarker-driven strategies that can identify unique patterns of drug resistance and sensitivity. “This will allow us to ... identify which patients, which drug, and at which time.”
The ACE trial was funded by Chipscreen Biosciences.
SOURCE: Jiang Z et al. ESMO 2018, Abstract 283O.
MUNICH – For patients with HR-positive (HR+) and human epidermal growth factor receptor 2 (HER2)–advanced breast cancer who have progressed after endocrine therapy, a combination of the oral histone deacetylase (HDAC) inhibitor chidamide and exemestane appears safe and more effective than exemestane alone, according to results from the phase 3 ACE trial.
“This is the first phase 3 trial to demonstrate that an HDAC inhibitor plus endocrine blockade improves progression-free survival, compared to endocrine blockade alone in hormone receptor positive advanced breast cancer patients who have progressed after prior endocrine therapy,” said lead author, Zefei Jiang, MD, at the European Society for Medical Oncology Congress.
HDAC inhibitors have historically been used for psychiatric and neurologic applications, but interest in their antineoplastic potential has increased over the past decade. Chidamide is approved for T-cell lymphoma in China, but not in the United States, where three other HDAC inhibitors are labeled for T-cell lymphoma, and a fourth is approved for multiple myeloma.
Although no HDAC inhibitors are clinically available for breast cancer, the future may tell a different story. The HDAC inhibitor entinostat received a breakthrough therapy designation by the Food and Drug Administration after the phase 2 ENCORE 301 trial showed clinical benefit (also with exemestane for advanced breast cancer). Ongoing studies are also evaluating the potential for HDAC inhibitors in combination with immunotherapy.
“Histone modulation by HDACs is a very important mechanism for epigenetic regulation,” said Dr. Jiang, of the 307th Hospital of Chinese People’s Liberation Army in Beijing, highlighting associations with breast cancer drug resistance. HDAC inhibition may be able to overcome this obstacle by resensitizing tumors to estrogen modulator therapy.
ACE was a double-blind, placebo-controlled study involving 362 patients with HR+/HER2–advanced breast cancer who failed endocrine therapy. Patients had previously received no more than one round of chemotherapy for advanced disease, and no more than four therapies total. The treatment group received either chidamide 30 mg twice weekly with exemestane 25 mg daily (n = 241) or exemestane with placebo (n = 121). Tumor assessments were performed every 8 weeks, and the primary endpoint was progression-free survival (PFS).
The addition of chidamide nearly doubled PFS (7.4 months vs. 3.8 months) and provided a hazard ratio of .75 (P = .0336). Objective response and clinical benefit rates also were increased. At the time of presentation, data were too immature for an overall survival rate.
The most common grade 3 or higher adverse events were hematologic: neutropenia (50.8%), thrombocytopenia (27.5%), and leukopenia (18.8%), all considerably higher than 2.5% for each in the placebo group.
These tolerability issues were expected, however, based on previous chidamide findings.
“Not surprisingly ... 33% of patients had their dose reduced, 50% their dose interrupted, and this is despite the biweekly schedule,” said invited discussant Rebecca Dent, MD, of the National Cancer Centre in Singapore. Despite these issues, Dr. Dent concluded that chidamide otherwise “appears to be quite well tolerated,” and showed meaningful results.
“We now have a second trial demonstrating ... clinical benefit from the addition of HDAC inhibitors to endocrine therapy in [HR+] advanced breast cancer,” Dr. Dent said. “HDAC inhibitors clearly warrant further investigation in earlier settings of [HR+] advanced breast cancer and ... yet to be defined ... subgroups, and obviously we anxiously await the phase 3 results of entinostat.”
In consideration of the future, Dr. Dent suggested that more studies are needed to develop subgroup-targeted therapies and optimize sequencing. “We’ve really underestimated the selective pressure of these treatments and how they impact our subsequent therapies,” she said.
Dr. Dent noted how these factors limit predictive relevance of study findings in clinical practice, in which patients with different treatment histories may have completely different responses to the same agent.
To overcome these obstacles, Dr. Dent encouraged development of biomarker-driven strategies that can identify unique patterns of drug resistance and sensitivity. “This will allow us to ... identify which patients, which drug, and at which time.”
The ACE trial was funded by Chipscreen Biosciences.
SOURCE: Jiang Z et al. ESMO 2018, Abstract 283O.
MUNICH – For patients with HR-positive (HR+) and human epidermal growth factor receptor 2 (HER2)–advanced breast cancer who have progressed after endocrine therapy, a combination of the oral histone deacetylase (HDAC) inhibitor chidamide and exemestane appears safe and more effective than exemestane alone, according to results from the phase 3 ACE trial.
“This is the first phase 3 trial to demonstrate that an HDAC inhibitor plus endocrine blockade improves progression-free survival, compared to endocrine blockade alone in hormone receptor positive advanced breast cancer patients who have progressed after prior endocrine therapy,” said lead author, Zefei Jiang, MD, at the European Society for Medical Oncology Congress.
HDAC inhibitors have historically been used for psychiatric and neurologic applications, but interest in their antineoplastic potential has increased over the past decade. Chidamide is approved for T-cell lymphoma in China, but not in the United States, where three other HDAC inhibitors are labeled for T-cell lymphoma, and a fourth is approved for multiple myeloma.
Although no HDAC inhibitors are clinically available for breast cancer, the future may tell a different story. The HDAC inhibitor entinostat received a breakthrough therapy designation by the Food and Drug Administration after the phase 2 ENCORE 301 trial showed clinical benefit (also with exemestane for advanced breast cancer). Ongoing studies are also evaluating the potential for HDAC inhibitors in combination with immunotherapy.
“Histone modulation by HDACs is a very important mechanism for epigenetic regulation,” said Dr. Jiang, of the 307th Hospital of Chinese People’s Liberation Army in Beijing, highlighting associations with breast cancer drug resistance. HDAC inhibition may be able to overcome this obstacle by resensitizing tumors to estrogen modulator therapy.
ACE was a double-blind, placebo-controlled study involving 362 patients with HR+/HER2–advanced breast cancer who failed endocrine therapy. Patients had previously received no more than one round of chemotherapy for advanced disease, and no more than four therapies total. The treatment group received either chidamide 30 mg twice weekly with exemestane 25 mg daily (n = 241) or exemestane with placebo (n = 121). Tumor assessments were performed every 8 weeks, and the primary endpoint was progression-free survival (PFS).
The addition of chidamide nearly doubled PFS (7.4 months vs. 3.8 months) and provided a hazard ratio of .75 (P = .0336). Objective response and clinical benefit rates also were increased. At the time of presentation, data were too immature for an overall survival rate.
The most common grade 3 or higher adverse events were hematologic: neutropenia (50.8%), thrombocytopenia (27.5%), and leukopenia (18.8%), all considerably higher than 2.5% for each in the placebo group.
These tolerability issues were expected, however, based on previous chidamide findings.
“Not surprisingly ... 33% of patients had their dose reduced, 50% their dose interrupted, and this is despite the biweekly schedule,” said invited discussant Rebecca Dent, MD, of the National Cancer Centre in Singapore. Despite these issues, Dr. Dent concluded that chidamide otherwise “appears to be quite well tolerated,” and showed meaningful results.
“We now have a second trial demonstrating ... clinical benefit from the addition of HDAC inhibitors to endocrine therapy in [HR+] advanced breast cancer,” Dr. Dent said. “HDAC inhibitors clearly warrant further investigation in earlier settings of [HR+] advanced breast cancer and ... yet to be defined ... subgroups, and obviously we anxiously await the phase 3 results of entinostat.”
In consideration of the future, Dr. Dent suggested that more studies are needed to develop subgroup-targeted therapies and optimize sequencing. “We’ve really underestimated the selective pressure of these treatments and how they impact our subsequent therapies,” she said.
Dr. Dent noted how these factors limit predictive relevance of study findings in clinical practice, in which patients with different treatment histories may have completely different responses to the same agent.
To overcome these obstacles, Dr. Dent encouraged development of biomarker-driven strategies that can identify unique patterns of drug resistance and sensitivity. “This will allow us to ... identify which patients, which drug, and at which time.”
The ACE trial was funded by Chipscreen Biosciences.
SOURCE: Jiang Z et al. ESMO 2018, Abstract 283O.
REPORTING FROM ESMO 2018
Key clinical point: For patients with HR+/HER2–advanced breast cancer who have progressed after endocrine therapy, a combination of oral HDAC inhibitor chidamide and exemestane appears safe and more effective than exemestane alone.
Major finding: Chidamide + exemestane combination therapy increased progression-free survival by about 4 months compared with exemestane monotherapy (7.4 months vs 3.8 months).
Study details: ACE was a phase 3, double-blind, placebo-controlled trial involving 362 patients with HR+/HER2–advanced breast cancer who failed endocrine therapy.
Disclosures: The study was funded by Chipscreen Biosciences.
Source: Jiang Z et al. ESMO 2018, Abstract 283O.
PALOMA-3: Overall survival better for endocrine-sensitive patients only
MUNICH – The combination of the cyclin-dependent kinase 4/6 inhibitor palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with longer overall survival of women with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer in the PALOMA-3 trial.
But the benefit seemed to be almost entirely limited to women with sensitivity to previous endocrine therapy; differences in overall survival among the entire cohort were not statistically significant, reported Massimo Cristofanilli, MD, of Northwestern University in Chicago, and his colleagues.
“These findings confirm that the use of palbociclib plus fulvestrant is a standard for care in patients with previously treated hormone receptor–positive, HER2-negative advanced breast cancer, he said in a briefing held prior to his presentation of the data at the European Society for Medical Oncology Congress.
The results were published simultaneously online in the New England Journal of Medicine.
Briefing discussant Nadia Harbeck, MD, is a breast cancer specialist with the University of Munich Medical Center, who is a coinvestigator of PALOMA-3, noted that there are currently three marketed cyclin-dependent kinase (CDK) 4/6 inhibitors and that all three have been shown to be associated with prolonged progression-free survival (PFS).
Yet, “there’s still a lot of uncertainty out there in the community whether to give these drugs, when to give these drugs, and also from the payers’ perspective, because there’s no overall survival, and I think this is now going to change,” she said.
“Ten months overall survival benefit in a CDK 4/6 inhibitor study in the second-line setting I think is unprecedented, and I think will change people’s hearts who weren’t quite sure, and I think we can now confidently say to our patients that this is the drug to take,” she added.
Dr. Cristofanilli discussed results of a prespecified analysis of overall survival from the previously reported trial.
Investigators enrolled 521 patients with HR-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy, and randomly assigned them to fulvestrant plus palbociclib or placebo.
In addition to looking at overall survival, the analysis included evaluation of the effects of palbociclib in women both with and without sensitivity to endocrine therapy, the presence or absence of visceral metastatic disease, and menopausal status. In addition, the analysis looked at the efficacy of therapies after disease progression, and safety of the respective regimens.
The median overall survival at a median follow-up of 44.8 months was 34.9 months with palbociclib/fulvestrant vs. 28 months for placebo/fulvestrant, translating into a stratified hazard ratio (HR) for death in the palbociclib arm of 0.81, but this difference was not statistically significant (P = .09). The unstratified HR was 0.79 (P = .05; the prespecified significance threshold was a two-sided P value of .047).
When they looked at the 410 patients with documented sensitivity to previous endocrine therapy, however, the investigators found a median OS of 39.7 months with palbociclib vs. 29.7 months with placebo. The HR for death with palbociclib in this subgroup was 0.72, with a 95% confidence interval indicating statistical significance.
In contrast, among 111 patients with documented intrinsic endocrine resistance, the median OS with palbociclib was actually lower than in the placebo group, albeit not significantly, at 20.2 vs. 26.2 months, respectively (HR, 1.14; P = .012 for interaction).
The median time to starting chemotherapy was 17.6 months in the palbociclib/fulvestrant group vs. 8.8 months in the placebo/fulvestrant group (HR, 0.58; P less than .001).
The safety profile of the combination was similar to that seen in the primary analysis of PALOMA-3. Grade 3 or 4 neutropenia occurred in 70% of patients on palbociclib vs. none of the patients on placebo. Other grade 3 or 4 events included anemia in 4% vs. 2%, thrombocytopenia in 3% vs. none, and febrile neutropenia in 1% vs. none.
Other grade 3 or greater events occurring with palbociclib in more than 2% of patients were infections, fatigue, and elevated aspartate aminotransferase levels.
Invited discussant Fatima Cardoso, MD, director of the breast unit of the Champalimaud Clinical Center in Lisbon, commented that PALOMA-3 was adequately powered for the primary endpoint of PFS, but not for a secondary overall survival endpoint.
She also raised questions that still need to be answered about the use of CDK 4/6 inhibitors with endocrine therapy in this population, including how to better identify which patients might benefit from the combination, whether the combination should be used in the first line or in subsequent lines of therapy, and whether it should be used in patients with or without prior endocrine therapy exposure.
Another unanswered question is whether disease progression accelerates after CDK 4/6 inhibitors are stopped.
“We need to confirm if this problem of post progression is true or not, and there may be a rationale to explore continuing beyond progression. This was a paradigm that changed in the HER2-positive population, and we now know that we need to continue to block the HER2 pathway, because if we don’t, the progression is faster. Will that apply here as well?,” she asked.
Hope S. Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, commented that patients in PALOMA-3 were allowed to have had chemotherapy, and there is evidence to suggest that prior chemotherapy is a risk factor for resistance to other therapies as well.
“So looking at patients with hormone-sensitive disease who have done their chemotherapy, seeing a survival benefit in any subset of patients with hormone receptor–positive disease getting a targeted agent is already pretty exciting,” she said in an interview.
Dr. Rugo was not involved in PALOMA-3.
PALOMA-3 was supported by Pfizer. Dr. Cristofanilli disclosed personal fees from Pfizer, Novartis, and Merus. Dr. Harbeck disclosed honoraria for consulting and lecturing for Pfizer and others. Dr. Cardoso has disclosed consulting fees and institutional support from Pfizer and others. Dr. Rugo has received fees/honoraria and other support for activities for Pfizer and others.
SOURCE: Turner NC et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1810527.
MUNICH – The combination of the cyclin-dependent kinase 4/6 inhibitor palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with longer overall survival of women with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer in the PALOMA-3 trial.
But the benefit seemed to be almost entirely limited to women with sensitivity to previous endocrine therapy; differences in overall survival among the entire cohort were not statistically significant, reported Massimo Cristofanilli, MD, of Northwestern University in Chicago, and his colleagues.
“These findings confirm that the use of palbociclib plus fulvestrant is a standard for care in patients with previously treated hormone receptor–positive, HER2-negative advanced breast cancer, he said in a briefing held prior to his presentation of the data at the European Society for Medical Oncology Congress.
The results were published simultaneously online in the New England Journal of Medicine.
Briefing discussant Nadia Harbeck, MD, is a breast cancer specialist with the University of Munich Medical Center, who is a coinvestigator of PALOMA-3, noted that there are currently three marketed cyclin-dependent kinase (CDK) 4/6 inhibitors and that all three have been shown to be associated with prolonged progression-free survival (PFS).
Yet, “there’s still a lot of uncertainty out there in the community whether to give these drugs, when to give these drugs, and also from the payers’ perspective, because there’s no overall survival, and I think this is now going to change,” she said.
“Ten months overall survival benefit in a CDK 4/6 inhibitor study in the second-line setting I think is unprecedented, and I think will change people’s hearts who weren’t quite sure, and I think we can now confidently say to our patients that this is the drug to take,” she added.
Dr. Cristofanilli discussed results of a prespecified analysis of overall survival from the previously reported trial.
Investigators enrolled 521 patients with HR-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy, and randomly assigned them to fulvestrant plus palbociclib or placebo.
In addition to looking at overall survival, the analysis included evaluation of the effects of palbociclib in women both with and without sensitivity to endocrine therapy, the presence or absence of visceral metastatic disease, and menopausal status. In addition, the analysis looked at the efficacy of therapies after disease progression, and safety of the respective regimens.
The median overall survival at a median follow-up of 44.8 months was 34.9 months with palbociclib/fulvestrant vs. 28 months for placebo/fulvestrant, translating into a stratified hazard ratio (HR) for death in the palbociclib arm of 0.81, but this difference was not statistically significant (P = .09). The unstratified HR was 0.79 (P = .05; the prespecified significance threshold was a two-sided P value of .047).
When they looked at the 410 patients with documented sensitivity to previous endocrine therapy, however, the investigators found a median OS of 39.7 months with palbociclib vs. 29.7 months with placebo. The HR for death with palbociclib in this subgroup was 0.72, with a 95% confidence interval indicating statistical significance.
In contrast, among 111 patients with documented intrinsic endocrine resistance, the median OS with palbociclib was actually lower than in the placebo group, albeit not significantly, at 20.2 vs. 26.2 months, respectively (HR, 1.14; P = .012 for interaction).
The median time to starting chemotherapy was 17.6 months in the palbociclib/fulvestrant group vs. 8.8 months in the placebo/fulvestrant group (HR, 0.58; P less than .001).
The safety profile of the combination was similar to that seen in the primary analysis of PALOMA-3. Grade 3 or 4 neutropenia occurred in 70% of patients on palbociclib vs. none of the patients on placebo. Other grade 3 or 4 events included anemia in 4% vs. 2%, thrombocytopenia in 3% vs. none, and febrile neutropenia in 1% vs. none.
Other grade 3 or greater events occurring with palbociclib in more than 2% of patients were infections, fatigue, and elevated aspartate aminotransferase levels.
Invited discussant Fatima Cardoso, MD, director of the breast unit of the Champalimaud Clinical Center in Lisbon, commented that PALOMA-3 was adequately powered for the primary endpoint of PFS, but not for a secondary overall survival endpoint.
She also raised questions that still need to be answered about the use of CDK 4/6 inhibitors with endocrine therapy in this population, including how to better identify which patients might benefit from the combination, whether the combination should be used in the first line or in subsequent lines of therapy, and whether it should be used in patients with or without prior endocrine therapy exposure.
Another unanswered question is whether disease progression accelerates after CDK 4/6 inhibitors are stopped.
“We need to confirm if this problem of post progression is true or not, and there may be a rationale to explore continuing beyond progression. This was a paradigm that changed in the HER2-positive population, and we now know that we need to continue to block the HER2 pathway, because if we don’t, the progression is faster. Will that apply here as well?,” she asked.
Hope S. Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, commented that patients in PALOMA-3 were allowed to have had chemotherapy, and there is evidence to suggest that prior chemotherapy is a risk factor for resistance to other therapies as well.
“So looking at patients with hormone-sensitive disease who have done their chemotherapy, seeing a survival benefit in any subset of patients with hormone receptor–positive disease getting a targeted agent is already pretty exciting,” she said in an interview.
Dr. Rugo was not involved in PALOMA-3.
PALOMA-3 was supported by Pfizer. Dr. Cristofanilli disclosed personal fees from Pfizer, Novartis, and Merus. Dr. Harbeck disclosed honoraria for consulting and lecturing for Pfizer and others. Dr. Cardoso has disclosed consulting fees and institutional support from Pfizer and others. Dr. Rugo has received fees/honoraria and other support for activities for Pfizer and others.
SOURCE: Turner NC et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1810527.
MUNICH – The combination of the cyclin-dependent kinase 4/6 inhibitor palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with longer overall survival of women with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer in the PALOMA-3 trial.
But the benefit seemed to be almost entirely limited to women with sensitivity to previous endocrine therapy; differences in overall survival among the entire cohort were not statistically significant, reported Massimo Cristofanilli, MD, of Northwestern University in Chicago, and his colleagues.
“These findings confirm that the use of palbociclib plus fulvestrant is a standard for care in patients with previously treated hormone receptor–positive, HER2-negative advanced breast cancer, he said in a briefing held prior to his presentation of the data at the European Society for Medical Oncology Congress.
The results were published simultaneously online in the New England Journal of Medicine.
Briefing discussant Nadia Harbeck, MD, is a breast cancer specialist with the University of Munich Medical Center, who is a coinvestigator of PALOMA-3, noted that there are currently three marketed cyclin-dependent kinase (CDK) 4/6 inhibitors and that all three have been shown to be associated with prolonged progression-free survival (PFS).
Yet, “there’s still a lot of uncertainty out there in the community whether to give these drugs, when to give these drugs, and also from the payers’ perspective, because there’s no overall survival, and I think this is now going to change,” she said.
“Ten months overall survival benefit in a CDK 4/6 inhibitor study in the second-line setting I think is unprecedented, and I think will change people’s hearts who weren’t quite sure, and I think we can now confidently say to our patients that this is the drug to take,” she added.
Dr. Cristofanilli discussed results of a prespecified analysis of overall survival from the previously reported trial.
Investigators enrolled 521 patients with HR-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy, and randomly assigned them to fulvestrant plus palbociclib or placebo.
In addition to looking at overall survival, the analysis included evaluation of the effects of palbociclib in women both with and without sensitivity to endocrine therapy, the presence or absence of visceral metastatic disease, and menopausal status. In addition, the analysis looked at the efficacy of therapies after disease progression, and safety of the respective regimens.
The median overall survival at a median follow-up of 44.8 months was 34.9 months with palbociclib/fulvestrant vs. 28 months for placebo/fulvestrant, translating into a stratified hazard ratio (HR) for death in the palbociclib arm of 0.81, but this difference was not statistically significant (P = .09). The unstratified HR was 0.79 (P = .05; the prespecified significance threshold was a two-sided P value of .047).
When they looked at the 410 patients with documented sensitivity to previous endocrine therapy, however, the investigators found a median OS of 39.7 months with palbociclib vs. 29.7 months with placebo. The HR for death with palbociclib in this subgroup was 0.72, with a 95% confidence interval indicating statistical significance.
In contrast, among 111 patients with documented intrinsic endocrine resistance, the median OS with palbociclib was actually lower than in the placebo group, albeit not significantly, at 20.2 vs. 26.2 months, respectively (HR, 1.14; P = .012 for interaction).
The median time to starting chemotherapy was 17.6 months in the palbociclib/fulvestrant group vs. 8.8 months in the placebo/fulvestrant group (HR, 0.58; P less than .001).
The safety profile of the combination was similar to that seen in the primary analysis of PALOMA-3. Grade 3 or 4 neutropenia occurred in 70% of patients on palbociclib vs. none of the patients on placebo. Other grade 3 or 4 events included anemia in 4% vs. 2%, thrombocytopenia in 3% vs. none, and febrile neutropenia in 1% vs. none.
Other grade 3 or greater events occurring with palbociclib in more than 2% of patients were infections, fatigue, and elevated aspartate aminotransferase levels.
Invited discussant Fatima Cardoso, MD, director of the breast unit of the Champalimaud Clinical Center in Lisbon, commented that PALOMA-3 was adequately powered for the primary endpoint of PFS, but not for a secondary overall survival endpoint.
She also raised questions that still need to be answered about the use of CDK 4/6 inhibitors with endocrine therapy in this population, including how to better identify which patients might benefit from the combination, whether the combination should be used in the first line or in subsequent lines of therapy, and whether it should be used in patients with or without prior endocrine therapy exposure.
Another unanswered question is whether disease progression accelerates after CDK 4/6 inhibitors are stopped.
“We need to confirm if this problem of post progression is true or not, and there may be a rationale to explore continuing beyond progression. This was a paradigm that changed in the HER2-positive population, and we now know that we need to continue to block the HER2 pathway, because if we don’t, the progression is faster. Will that apply here as well?,” she asked.
Hope S. Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, commented that patients in PALOMA-3 were allowed to have had chemotherapy, and there is evidence to suggest that prior chemotherapy is a risk factor for resistance to other therapies as well.
“So looking at patients with hormone-sensitive disease who have done their chemotherapy, seeing a survival benefit in any subset of patients with hormone receptor–positive disease getting a targeted agent is already pretty exciting,” she said in an interview.
Dr. Rugo was not involved in PALOMA-3.
PALOMA-3 was supported by Pfizer. Dr. Cristofanilli disclosed personal fees from Pfizer, Novartis, and Merus. Dr. Harbeck disclosed honoraria for consulting and lecturing for Pfizer and others. Dr. Cardoso has disclosed consulting fees and institutional support from Pfizer and others. Dr. Rugo has received fees/honoraria and other support for activities for Pfizer and others.
SOURCE: Turner NC et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1810527.
AT ESMO 2018
Key clinical point: The combination of a CDK 4/6 inhibitor and a selective estrogen receptor modifier is associated with longer overall survival in some patients.
Major finding: Median OS 39.7 months with palbociclib/fulvestrant vs. 29.7 months with placebo/fulvestrant.
Study details: Prespecified survival analysis of 521 patients in the PALOMA-3 trial.
Disclosures: PALOMA-3 was supported by Pfizer. Dr. Cristofanilli disclosed personal fees from Pfizer, Novartis, and Merus. Dr. Harbeck disclosed honoraria for consulting and lecturing for Pfizer and others. Dr. Cardoso has disclosed consulting fees and institutional support from Pfizer and others. Dr. Rugo has received fees/honoraria and other support for activities for Pfizer and others.
Source: Turner NC et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1810527.
Finally, immunotherapy shows benefit in TNBC
MUNICH – For the first time, a combination of an immune checkpoint inhibitor and a taxane has shown significant clinical benefit in patients with metastatic triple-negative breast cancer in a phase 3 trial, but the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), investigators reported.
Among 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)-paclitaxel or placebo plus nab-paclitaxel, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease in an interim analysis of the IMpassion 130 trial.
However, although there was a significant progression-free survival (PFS) benefit with atezolizumab in an intention-to-treat (ITT) analysis that included patients with PD-L1 negative tumors, there was no significant difference in median overall survival (OS) when all patients were considered together, said Peter Schmid, MD, PhD, Barts Cancer Institute, Queen Mary University of London.
“For patients with PD-L1–positive tumors, these data establish atezolizumab and nab-paclitaxel as a new standard of care,” he said at the European Society for Medical Oncology Congress.
The results were published online in the New England Journal of Medicine to coincide with the presentation of the data.
At a briefing prior to presentation of the data in a symposium, discussant Nadia Harbeck, MD, of the University of Munich Medical Center, a breast cancer specialist, confessed to being of envious of her colleagues in other oncology specialties in which immunotherapy has made great inroads.
“We have a lot of patients out there right now in clinical trials with immune therapy, but so far in breast cancer, we have not seen the tremendous effects we have seen in melanoma or lung cancer, so this is the first time we have a phase 3 trial proving that immune therapy in triple-negative breast cancer improves survival, and I think this is something that will change the way we practice in triple-negative breast cancer,” she said.
The rationale for using a PD-L1 inhibitor comes from the discovery that PD-L1 expression occurs primarily on tumor-infiltrating cells in TNBC rather than on tumor cells, which can inhibit immune responses directed against tumors.
The investigators enrolled 902 patients with previously untreated mTNBC and randomly assigned them to receive nab-paclitaxel 100 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle, plus either atezolizumab 804 mg intravenously or placebo on days 1 and 15 of each cycle.
Patients were stratified according to whether they received neoadjuvant or adjuvant taxane therapy, the presence of liver metastases at baseline, and PD-L1 expression at baseline.
Treatment was continued until disease progression or unacceptable toxicity.
The primary endpoints were PFS and OS in both the ITT and PD-L1–positive population.
In the ITT analysis, 1-year PFS rate was significantly improved in the atezolizumab arm, at 24% vs. 18% in the placebo arm. This translated into a stratified hazard ratio of 0.80 (P = .0025).
In the analysis restricted to the PD-L1-positive population (369 patients), the 1-year PFS rates were 29% for atezolizumab vs. 16% for placebo, translating into to an HR of 0.62 (P less than .0001).
As noted before, the interim OS analysis in the PD-L1 population showed a clinical benefit with atezolizumab, with a 2-year OS rate of 54% vs. 37%, respectively. The median OS in this analysis was 25 months with atezolizumab, vs. 15.5 months with placebo. The stratified HR favoring the PD-L1 inhibitor was 0.62, but because of the hierarchical statistical analysis design of the trial, formal testing of OS was not performed for the interim analysis.
Adverse events of any kind occurred in 99.3% of patients assigned to atezolizumab/nab-paclitaxel and 97.9% of those assigned to placebo/nab-paclitaxel.
Grade 1 or 2 immune-related hypothyroidism occurred more frequently with atezolizumab (17.3% vs. 4.3%), but none led to discontinuation of the drug regimen.
Six patients assigned to atezolizumab and three assigned to placebo died. Four of the deaths were deemed by investigators to be related to the trial regimen, include three deaths in the atezolizumab arm (from autoimmune hepatitis, mucosal inflammation, and septic shock), and one death in the placebo arm (from hepatic failure).
“A benefit with atezolizumab/nab-paclitaxel in patients with PD-L1–positive tumors that was shown in our trial provides evidence of the efficacy of immunotherapy in at least a subset of patients. It is important for patients’ PD-L1 expression status on tumor-infiltrating immune cells to be taken into consideration to inform treatment choices for patients with metastatic triple-negative breast cancer,” Dr. Schmid and his colleagues wrote in the study’s conclusion.
“I really do think that these results are going to make a very big difference,” said coinvestigator Hope S. Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.
“We believed from the phase 1 data and the less-than-exciting phase 2 data that there was clearly some role for immunotherapy in breast cancer but were really struggling as to what that role was. We knew for example that if they had a response, patients lived longer and really dramatically longer,” she said in an interview.
But unlike the clinical revolution brought about by the introduction of trastuzumab, in which clinicians had a biomarker and a large number of patients benefited, “here we have no biomarker and a small number of patients benefited, but the benefit is huge,” she said.
Giuseppe Curigliano, MD, PhD, from the University of Milan and European Cancer Institute, Italy, the invited discussant at the symposium, agreed that the study “brings breast cancer into the immunotherapy era.”
Dr. Curigliano added, however, that the study was missing an arm – atezolizumab alone, which might be a good option for a subset of patients.
He also questioned whether nab-paclitaxel was the best partner for atezolizumab, vs. other drugs with known immunogenic effects, such as doxorubicin, cyclophosphamide, other taxanes, gemcitabine, or platinum salts.
The study was supported by F. Hoffmann–La Roche/Genentech. Dr. Schmid reported grant and nonfinancial support from Roche. Multiple coauthors reported financial relationships with Roche/Genentech and others. Dr. Harbeck has disclosed honoraria from and serving as a consultant for Roche and others. Dr. Rugo disclosed grants and nonfinancial support from F. Hoffmann–La Roche. Dr. Curigliano disclosed consulting/advising, speakers bureau participation, and travel/accommodations from Roche/Genentech.
SOURCE: Schmid P et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1809615.
MUNICH – For the first time, a combination of an immune checkpoint inhibitor and a taxane has shown significant clinical benefit in patients with metastatic triple-negative breast cancer in a phase 3 trial, but the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), investigators reported.
Among 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)-paclitaxel or placebo plus nab-paclitaxel, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease in an interim analysis of the IMpassion 130 trial.
However, although there was a significant progression-free survival (PFS) benefit with atezolizumab in an intention-to-treat (ITT) analysis that included patients with PD-L1 negative tumors, there was no significant difference in median overall survival (OS) when all patients were considered together, said Peter Schmid, MD, PhD, Barts Cancer Institute, Queen Mary University of London.
“For patients with PD-L1–positive tumors, these data establish atezolizumab and nab-paclitaxel as a new standard of care,” he said at the European Society for Medical Oncology Congress.
The results were published online in the New England Journal of Medicine to coincide with the presentation of the data.
At a briefing prior to presentation of the data in a symposium, discussant Nadia Harbeck, MD, of the University of Munich Medical Center, a breast cancer specialist, confessed to being of envious of her colleagues in other oncology specialties in which immunotherapy has made great inroads.
“We have a lot of patients out there right now in clinical trials with immune therapy, but so far in breast cancer, we have not seen the tremendous effects we have seen in melanoma or lung cancer, so this is the first time we have a phase 3 trial proving that immune therapy in triple-negative breast cancer improves survival, and I think this is something that will change the way we practice in triple-negative breast cancer,” she said.
The rationale for using a PD-L1 inhibitor comes from the discovery that PD-L1 expression occurs primarily on tumor-infiltrating cells in TNBC rather than on tumor cells, which can inhibit immune responses directed against tumors.
The investigators enrolled 902 patients with previously untreated mTNBC and randomly assigned them to receive nab-paclitaxel 100 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle, plus either atezolizumab 804 mg intravenously or placebo on days 1 and 15 of each cycle.
Patients were stratified according to whether they received neoadjuvant or adjuvant taxane therapy, the presence of liver metastases at baseline, and PD-L1 expression at baseline.
Treatment was continued until disease progression or unacceptable toxicity.
The primary endpoints were PFS and OS in both the ITT and PD-L1–positive population.
In the ITT analysis, 1-year PFS rate was significantly improved in the atezolizumab arm, at 24% vs. 18% in the placebo arm. This translated into a stratified hazard ratio of 0.80 (P = .0025).
In the analysis restricted to the PD-L1-positive population (369 patients), the 1-year PFS rates were 29% for atezolizumab vs. 16% for placebo, translating into to an HR of 0.62 (P less than .0001).
As noted before, the interim OS analysis in the PD-L1 population showed a clinical benefit with atezolizumab, with a 2-year OS rate of 54% vs. 37%, respectively. The median OS in this analysis was 25 months with atezolizumab, vs. 15.5 months with placebo. The stratified HR favoring the PD-L1 inhibitor was 0.62, but because of the hierarchical statistical analysis design of the trial, formal testing of OS was not performed for the interim analysis.
Adverse events of any kind occurred in 99.3% of patients assigned to atezolizumab/nab-paclitaxel and 97.9% of those assigned to placebo/nab-paclitaxel.
Grade 1 or 2 immune-related hypothyroidism occurred more frequently with atezolizumab (17.3% vs. 4.3%), but none led to discontinuation of the drug regimen.
Six patients assigned to atezolizumab and three assigned to placebo died. Four of the deaths were deemed by investigators to be related to the trial regimen, include three deaths in the atezolizumab arm (from autoimmune hepatitis, mucosal inflammation, and septic shock), and one death in the placebo arm (from hepatic failure).
“A benefit with atezolizumab/nab-paclitaxel in patients with PD-L1–positive tumors that was shown in our trial provides evidence of the efficacy of immunotherapy in at least a subset of patients. It is important for patients’ PD-L1 expression status on tumor-infiltrating immune cells to be taken into consideration to inform treatment choices for patients with metastatic triple-negative breast cancer,” Dr. Schmid and his colleagues wrote in the study’s conclusion.
“I really do think that these results are going to make a very big difference,” said coinvestigator Hope S. Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.
“We believed from the phase 1 data and the less-than-exciting phase 2 data that there was clearly some role for immunotherapy in breast cancer but were really struggling as to what that role was. We knew for example that if they had a response, patients lived longer and really dramatically longer,” she said in an interview.
But unlike the clinical revolution brought about by the introduction of trastuzumab, in which clinicians had a biomarker and a large number of patients benefited, “here we have no biomarker and a small number of patients benefited, but the benefit is huge,” she said.
Giuseppe Curigliano, MD, PhD, from the University of Milan and European Cancer Institute, Italy, the invited discussant at the symposium, agreed that the study “brings breast cancer into the immunotherapy era.”
Dr. Curigliano added, however, that the study was missing an arm – atezolizumab alone, which might be a good option for a subset of patients.
He also questioned whether nab-paclitaxel was the best partner for atezolizumab, vs. other drugs with known immunogenic effects, such as doxorubicin, cyclophosphamide, other taxanes, gemcitabine, or platinum salts.
The study was supported by F. Hoffmann–La Roche/Genentech. Dr. Schmid reported grant and nonfinancial support from Roche. Multiple coauthors reported financial relationships with Roche/Genentech and others. Dr. Harbeck has disclosed honoraria from and serving as a consultant for Roche and others. Dr. Rugo disclosed grants and nonfinancial support from F. Hoffmann–La Roche. Dr. Curigliano disclosed consulting/advising, speakers bureau participation, and travel/accommodations from Roche/Genentech.
SOURCE: Schmid P et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1809615.
MUNICH – For the first time, a combination of an immune checkpoint inhibitor and a taxane has shown significant clinical benefit in patients with metastatic triple-negative breast cancer in a phase 3 trial, but the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), investigators reported.
Among 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)-paclitaxel or placebo plus nab-paclitaxel, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease in an interim analysis of the IMpassion 130 trial.
However, although there was a significant progression-free survival (PFS) benefit with atezolizumab in an intention-to-treat (ITT) analysis that included patients with PD-L1 negative tumors, there was no significant difference in median overall survival (OS) when all patients were considered together, said Peter Schmid, MD, PhD, Barts Cancer Institute, Queen Mary University of London.
“For patients with PD-L1–positive tumors, these data establish atezolizumab and nab-paclitaxel as a new standard of care,” he said at the European Society for Medical Oncology Congress.
The results were published online in the New England Journal of Medicine to coincide with the presentation of the data.
At a briefing prior to presentation of the data in a symposium, discussant Nadia Harbeck, MD, of the University of Munich Medical Center, a breast cancer specialist, confessed to being of envious of her colleagues in other oncology specialties in which immunotherapy has made great inroads.
“We have a lot of patients out there right now in clinical trials with immune therapy, but so far in breast cancer, we have not seen the tremendous effects we have seen in melanoma or lung cancer, so this is the first time we have a phase 3 trial proving that immune therapy in triple-negative breast cancer improves survival, and I think this is something that will change the way we practice in triple-negative breast cancer,” she said.
The rationale for using a PD-L1 inhibitor comes from the discovery that PD-L1 expression occurs primarily on tumor-infiltrating cells in TNBC rather than on tumor cells, which can inhibit immune responses directed against tumors.
The investigators enrolled 902 patients with previously untreated mTNBC and randomly assigned them to receive nab-paclitaxel 100 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle, plus either atezolizumab 804 mg intravenously or placebo on days 1 and 15 of each cycle.
Patients were stratified according to whether they received neoadjuvant or adjuvant taxane therapy, the presence of liver metastases at baseline, and PD-L1 expression at baseline.
Treatment was continued until disease progression or unacceptable toxicity.
The primary endpoints were PFS and OS in both the ITT and PD-L1–positive population.
In the ITT analysis, 1-year PFS rate was significantly improved in the atezolizumab arm, at 24% vs. 18% in the placebo arm. This translated into a stratified hazard ratio of 0.80 (P = .0025).
In the analysis restricted to the PD-L1-positive population (369 patients), the 1-year PFS rates were 29% for atezolizumab vs. 16% for placebo, translating into to an HR of 0.62 (P less than .0001).
As noted before, the interim OS analysis in the PD-L1 population showed a clinical benefit with atezolizumab, with a 2-year OS rate of 54% vs. 37%, respectively. The median OS in this analysis was 25 months with atezolizumab, vs. 15.5 months with placebo. The stratified HR favoring the PD-L1 inhibitor was 0.62, but because of the hierarchical statistical analysis design of the trial, formal testing of OS was not performed for the interim analysis.
Adverse events of any kind occurred in 99.3% of patients assigned to atezolizumab/nab-paclitaxel and 97.9% of those assigned to placebo/nab-paclitaxel.
Grade 1 or 2 immune-related hypothyroidism occurred more frequently with atezolizumab (17.3% vs. 4.3%), but none led to discontinuation of the drug regimen.
Six patients assigned to atezolizumab and three assigned to placebo died. Four of the deaths were deemed by investigators to be related to the trial regimen, include three deaths in the atezolizumab arm (from autoimmune hepatitis, mucosal inflammation, and septic shock), and one death in the placebo arm (from hepatic failure).
“A benefit with atezolizumab/nab-paclitaxel in patients with PD-L1–positive tumors that was shown in our trial provides evidence of the efficacy of immunotherapy in at least a subset of patients. It is important for patients’ PD-L1 expression status on tumor-infiltrating immune cells to be taken into consideration to inform treatment choices for patients with metastatic triple-negative breast cancer,” Dr. Schmid and his colleagues wrote in the study’s conclusion.
“I really do think that these results are going to make a very big difference,” said coinvestigator Hope S. Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.
“We believed from the phase 1 data and the less-than-exciting phase 2 data that there was clearly some role for immunotherapy in breast cancer but were really struggling as to what that role was. We knew for example that if they had a response, patients lived longer and really dramatically longer,” she said in an interview.
But unlike the clinical revolution brought about by the introduction of trastuzumab, in which clinicians had a biomarker and a large number of patients benefited, “here we have no biomarker and a small number of patients benefited, but the benefit is huge,” she said.
Giuseppe Curigliano, MD, PhD, from the University of Milan and European Cancer Institute, Italy, the invited discussant at the symposium, agreed that the study “brings breast cancer into the immunotherapy era.”
Dr. Curigliano added, however, that the study was missing an arm – atezolizumab alone, which might be a good option for a subset of patients.
He also questioned whether nab-paclitaxel was the best partner for atezolizumab, vs. other drugs with known immunogenic effects, such as doxorubicin, cyclophosphamide, other taxanes, gemcitabine, or platinum salts.
The study was supported by F. Hoffmann–La Roche/Genentech. Dr. Schmid reported grant and nonfinancial support from Roche. Multiple coauthors reported financial relationships with Roche/Genentech and others. Dr. Harbeck has disclosed honoraria from and serving as a consultant for Roche and others. Dr. Rugo disclosed grants and nonfinancial support from F. Hoffmann–La Roche. Dr. Curigliano disclosed consulting/advising, speakers bureau participation, and travel/accommodations from Roche/Genentech.
SOURCE: Schmid P et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1809615.
AT ESMO 2018
Key clinical point: IMpassion 130 is the first phase 3 trial to show a benefit of immunotherapy in triple-negative breast cancer.
Major finding: Progression-free and overall survival were significantly improved with atezolizumab in the PD-L1–positive population.
Study details: Randomized phase 3 trial in 902 patients with triple-negative breast cancer.
Disclosures: The study was supported by F. Hoffmann–La Roche/Genentech. Dr. Schmid reported grant and nonfinancial support from Roche. Multiple coauthors reported financial relationships with Roche/Genentech and others. Dr. Harbeck has disclosed honoraria from and serving as a consultant for Roche and others. Dr. Rugo disclosed grants and nonfinancial support from F. Hoffmann–La Roche. Dr. Curigliano disclosed consulting/advising, speakers bureau participation, and travel/accommodations from Roche/Genentech.
Source: Schmid P et al. N Engl J Med. 2018 Oct 20. doi: 10.1056/NEJMoa1809615.
Genotype-driven dosing reduces 5-FU, capecitabine toxicity
MUNICH – Pretreatment genotyping of patients for a key metabolizing enzyme prior to therapy with a fluoropyrimidine agent can be performed in routine clinical practice and can significantly improve safety of the drugs, investigators reported.
Among 1,103 patients scheduled for fluoropyrimidine-based therapy with either fluorouracil (5-FU) or capecitabine alone or in combination with other therapies, toxicities were highest among patients with two common variant alleles of DPYD, the gene encoding for the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). The risk for toxicity was “markedly reduced” when doses were reduced by 50% in patients carrying the alleles, reported Linda Henricks, PharmD, from the Netherlands Cancer Institute, Amsterdam, and her colleagues.
“Our study was done in a daily clinical care setting in regional general hospitals and a few academic centers, showing the feasibility of implementation of upfront DPYD screening. To make DPYD-guided dosing feasible in all hospitals, the turnaround time for DPYD genotyping must be short to prevent a delay in the start of treatment,” they wrote in a study published in The Lancet Oncology prior to presentation of these data at the European Society of Medical Oncology Congress.
The laboratories participating in their study had turnaround times ranging from a few days up to 1 week, they noted.
Fluoropyrimidines are the backbones of therapy for several different malignancies, but up to 30% of patients treated with these drugs can experience severe toxicities because of reduced DPD activity, primarily caused by genetic variants in DPYD.
The investigators conducted a prospective multicenter study to see whether screening for the four most common variants could help clinicians tailor treatment programs to improve tolerability of fluoropyrimidine-based therapies.
They looked at the incidence of toxicities between patients carrying DPYD variant alleles and DPYD wild-type carriers in an intention-to-treat analysis, and compared relative risks for severe toxicities among patients with those of historical controls – patients with DPYD variant alleles who had been treated with a full-dose fluoropyrimidine in previous studies.
They enrolled 1,181 patients during May 2015–December 2017, of whom 1,103 were evaluable. Of this group, 92% (1,018 patients) had wild-type DPYD, and 8% (85) were heterozygous variant allele carriers.
The four variant alleles the investigators genotyped for were: DPYD*2A, c.2846A>T, c.1679T>G, and c.1236G>A.
Patients who were heterozygous for c.2846A>T or c.1236G>A received doses reduced by 25%, and patients with DPYD*2A or c.1679T>G received doses reduced by 50%. Patients with DPYD wild-type were treated according to the current standard of care.
The incidence of severe fluoropyrimidine-related toxicity, the primary endpoint, was significantly higher among variant allele carriers compared with patients with wild-type DPYD (39% vs. 23%, respectively, P = .0013).
The relative risk for severe toxicity among patients with DPYD*2A treated in the current study with genotype-guided therapy was 1.31, compared with 2.87 for historical controls carrying the same variant.
Among c.1679T>G carriers, those treated with genotype-guided therapy had no severe toxicity, whereas the relative risk for historical controls was 4.30.
Respective relative risks for c.2846A>T carriers were 2.0 vs. 3.11, and for c.1236G>A carriers were 1.69 vs. 1.72.
“Although our study revealed that the applied approach of genotype-guided adaptive dosing significantly reduced severe fluoropyrimidine-induced toxicity and prevented treatment-related death, additional methods should be explored and prospectively tested to further reduce treatment-related toxicity, not only in DPYD variant allele carriers, but also in DPYD wild-type patients,” Dr. Henricks and her associates wrote.
The study was supported by the Dutch Cancer Society. Dr. Henricks and a coauthor report grants from the Society. One coauthor reported a prior unrestricted grant from Roche and one personal fee from Modra outside the submitted work.
SOURCE: Henricks LM et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30686-7.
Therapeutic drug monitoring provides an alternative to guide dose adaptations. For capecitabine, because of the intracellular conversion of this prodrug into fluorouracil (5-FU) and cytotoxic metabolites, the utility of therapeutic drug monitoring for dose optimization is unclear. By contrast, therapeutic drug monitoring is well established for infusional 5-FU, with defined target ranges and dosing algorithms available. Therefore, to prevent toxicities during dose escalation, dose titration in DPYD risk variant carriers could be done using infusional 5-FU with a starting dose of 50%, followed by therapeutic drug monitoring.
Prospective evaluation of genotype-guided dosing has been done for very few pharmacogenetic markers. With two prospective studies showing both feasibility and clinical benefit, DPYD genotyping provides a leading example of how prospective pharmacogenetic testing can result in benefits for patients by reducing morbidity and mortality associated with adverse drug effects. With fluoropyrimidines remaining a mainstay of cancer chemotherapy, these benefits will continue to be of relevance for the foreseeable future.
Ursula Amstutz, PhD, and Carlo R Largiadèr, PhD, are from the University Institute of Clinical Chemistry at the University of Bern, Switzerland. Their comments were adapted from an editorial accompanying the study in The Lancet: Oncology. They reported no competing interests.
Therapeutic drug monitoring provides an alternative to guide dose adaptations. For capecitabine, because of the intracellular conversion of this prodrug into fluorouracil (5-FU) and cytotoxic metabolites, the utility of therapeutic drug monitoring for dose optimization is unclear. By contrast, therapeutic drug monitoring is well established for infusional 5-FU, with defined target ranges and dosing algorithms available. Therefore, to prevent toxicities during dose escalation, dose titration in DPYD risk variant carriers could be done using infusional 5-FU with a starting dose of 50%, followed by therapeutic drug monitoring.
Prospective evaluation of genotype-guided dosing has been done for very few pharmacogenetic markers. With two prospective studies showing both feasibility and clinical benefit, DPYD genotyping provides a leading example of how prospective pharmacogenetic testing can result in benefits for patients by reducing morbidity and mortality associated with adverse drug effects. With fluoropyrimidines remaining a mainstay of cancer chemotherapy, these benefits will continue to be of relevance for the foreseeable future.
Ursula Amstutz, PhD, and Carlo R Largiadèr, PhD, are from the University Institute of Clinical Chemistry at the University of Bern, Switzerland. Their comments were adapted from an editorial accompanying the study in The Lancet: Oncology. They reported no competing interests.
Therapeutic drug monitoring provides an alternative to guide dose adaptations. For capecitabine, because of the intracellular conversion of this prodrug into fluorouracil (5-FU) and cytotoxic metabolites, the utility of therapeutic drug monitoring for dose optimization is unclear. By contrast, therapeutic drug monitoring is well established for infusional 5-FU, with defined target ranges and dosing algorithms available. Therefore, to prevent toxicities during dose escalation, dose titration in DPYD risk variant carriers could be done using infusional 5-FU with a starting dose of 50%, followed by therapeutic drug monitoring.
Prospective evaluation of genotype-guided dosing has been done for very few pharmacogenetic markers. With two prospective studies showing both feasibility and clinical benefit, DPYD genotyping provides a leading example of how prospective pharmacogenetic testing can result in benefits for patients by reducing morbidity and mortality associated with adverse drug effects. With fluoropyrimidines remaining a mainstay of cancer chemotherapy, these benefits will continue to be of relevance for the foreseeable future.
Ursula Amstutz, PhD, and Carlo R Largiadèr, PhD, are from the University Institute of Clinical Chemistry at the University of Bern, Switzerland. Their comments were adapted from an editorial accompanying the study in The Lancet: Oncology. They reported no competing interests.
MUNICH – Pretreatment genotyping of patients for a key metabolizing enzyme prior to therapy with a fluoropyrimidine agent can be performed in routine clinical practice and can significantly improve safety of the drugs, investigators reported.
Among 1,103 patients scheduled for fluoropyrimidine-based therapy with either fluorouracil (5-FU) or capecitabine alone or in combination with other therapies, toxicities were highest among patients with two common variant alleles of DPYD, the gene encoding for the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). The risk for toxicity was “markedly reduced” when doses were reduced by 50% in patients carrying the alleles, reported Linda Henricks, PharmD, from the Netherlands Cancer Institute, Amsterdam, and her colleagues.
“Our study was done in a daily clinical care setting in regional general hospitals and a few academic centers, showing the feasibility of implementation of upfront DPYD screening. To make DPYD-guided dosing feasible in all hospitals, the turnaround time for DPYD genotyping must be short to prevent a delay in the start of treatment,” they wrote in a study published in The Lancet Oncology prior to presentation of these data at the European Society of Medical Oncology Congress.
The laboratories participating in their study had turnaround times ranging from a few days up to 1 week, they noted.
Fluoropyrimidines are the backbones of therapy for several different malignancies, but up to 30% of patients treated with these drugs can experience severe toxicities because of reduced DPD activity, primarily caused by genetic variants in DPYD.
The investigators conducted a prospective multicenter study to see whether screening for the four most common variants could help clinicians tailor treatment programs to improve tolerability of fluoropyrimidine-based therapies.
They looked at the incidence of toxicities between patients carrying DPYD variant alleles and DPYD wild-type carriers in an intention-to-treat analysis, and compared relative risks for severe toxicities among patients with those of historical controls – patients with DPYD variant alleles who had been treated with a full-dose fluoropyrimidine in previous studies.
They enrolled 1,181 patients during May 2015–December 2017, of whom 1,103 were evaluable. Of this group, 92% (1,018 patients) had wild-type DPYD, and 8% (85) were heterozygous variant allele carriers.
The four variant alleles the investigators genotyped for were: DPYD*2A, c.2846A>T, c.1679T>G, and c.1236G>A.
Patients who were heterozygous for c.2846A>T or c.1236G>A received doses reduced by 25%, and patients with DPYD*2A or c.1679T>G received doses reduced by 50%. Patients with DPYD wild-type were treated according to the current standard of care.
The incidence of severe fluoropyrimidine-related toxicity, the primary endpoint, was significantly higher among variant allele carriers compared with patients with wild-type DPYD (39% vs. 23%, respectively, P = .0013).
The relative risk for severe toxicity among patients with DPYD*2A treated in the current study with genotype-guided therapy was 1.31, compared with 2.87 for historical controls carrying the same variant.
Among c.1679T>G carriers, those treated with genotype-guided therapy had no severe toxicity, whereas the relative risk for historical controls was 4.30.
Respective relative risks for c.2846A>T carriers were 2.0 vs. 3.11, and for c.1236G>A carriers were 1.69 vs. 1.72.
“Although our study revealed that the applied approach of genotype-guided adaptive dosing significantly reduced severe fluoropyrimidine-induced toxicity and prevented treatment-related death, additional methods should be explored and prospectively tested to further reduce treatment-related toxicity, not only in DPYD variant allele carriers, but also in DPYD wild-type patients,” Dr. Henricks and her associates wrote.
The study was supported by the Dutch Cancer Society. Dr. Henricks and a coauthor report grants from the Society. One coauthor reported a prior unrestricted grant from Roche and one personal fee from Modra outside the submitted work.
SOURCE: Henricks LM et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30686-7.
MUNICH – Pretreatment genotyping of patients for a key metabolizing enzyme prior to therapy with a fluoropyrimidine agent can be performed in routine clinical practice and can significantly improve safety of the drugs, investigators reported.
Among 1,103 patients scheduled for fluoropyrimidine-based therapy with either fluorouracil (5-FU) or capecitabine alone or in combination with other therapies, toxicities were highest among patients with two common variant alleles of DPYD, the gene encoding for the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). The risk for toxicity was “markedly reduced” when doses were reduced by 50% in patients carrying the alleles, reported Linda Henricks, PharmD, from the Netherlands Cancer Institute, Amsterdam, and her colleagues.
“Our study was done in a daily clinical care setting in regional general hospitals and a few academic centers, showing the feasibility of implementation of upfront DPYD screening. To make DPYD-guided dosing feasible in all hospitals, the turnaround time for DPYD genotyping must be short to prevent a delay in the start of treatment,” they wrote in a study published in The Lancet Oncology prior to presentation of these data at the European Society of Medical Oncology Congress.
The laboratories participating in their study had turnaround times ranging from a few days up to 1 week, they noted.
Fluoropyrimidines are the backbones of therapy for several different malignancies, but up to 30% of patients treated with these drugs can experience severe toxicities because of reduced DPD activity, primarily caused by genetic variants in DPYD.
The investigators conducted a prospective multicenter study to see whether screening for the four most common variants could help clinicians tailor treatment programs to improve tolerability of fluoropyrimidine-based therapies.
They looked at the incidence of toxicities between patients carrying DPYD variant alleles and DPYD wild-type carriers in an intention-to-treat analysis, and compared relative risks for severe toxicities among patients with those of historical controls – patients with DPYD variant alleles who had been treated with a full-dose fluoropyrimidine in previous studies.
They enrolled 1,181 patients during May 2015–December 2017, of whom 1,103 were evaluable. Of this group, 92% (1,018 patients) had wild-type DPYD, and 8% (85) were heterozygous variant allele carriers.
The four variant alleles the investigators genotyped for were: DPYD*2A, c.2846A>T, c.1679T>G, and c.1236G>A.
Patients who were heterozygous for c.2846A>T or c.1236G>A received doses reduced by 25%, and patients with DPYD*2A or c.1679T>G received doses reduced by 50%. Patients with DPYD wild-type were treated according to the current standard of care.
The incidence of severe fluoropyrimidine-related toxicity, the primary endpoint, was significantly higher among variant allele carriers compared with patients with wild-type DPYD (39% vs. 23%, respectively, P = .0013).
The relative risk for severe toxicity among patients with DPYD*2A treated in the current study with genotype-guided therapy was 1.31, compared with 2.87 for historical controls carrying the same variant.
Among c.1679T>G carriers, those treated with genotype-guided therapy had no severe toxicity, whereas the relative risk for historical controls was 4.30.
Respective relative risks for c.2846A>T carriers were 2.0 vs. 3.11, and for c.1236G>A carriers were 1.69 vs. 1.72.
“Although our study revealed that the applied approach of genotype-guided adaptive dosing significantly reduced severe fluoropyrimidine-induced toxicity and prevented treatment-related death, additional methods should be explored and prospectively tested to further reduce treatment-related toxicity, not only in DPYD variant allele carriers, but also in DPYD wild-type patients,” Dr. Henricks and her associates wrote.
The study was supported by the Dutch Cancer Society. Dr. Henricks and a coauthor report grants from the Society. One coauthor reported a prior unrestricted grant from Roche and one personal fee from Modra outside the submitted work.
SOURCE: Henricks LM et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30686-7.
AT ESMO 2018
Key clinical point: Variant alleles in the gene DPYD are associated with higher risk for fluoropyrimidine-associated toxicity.
Major finding: Genotype-guided adaptive dosing was associated with lower risk of severe toxicity, compared with historical controls.
Study details: Prospective multicenter study of 1,103 patients scheduled to be treated with fluorouracil or capecitabine as monotherapy or in combination.
Disclosures: The study was supported by the Dutch Cancer Society. Dr. Henricks and a coauthor reported grants from the Society. One coauthor reported a prior unrestricted grant from Roche and one personal fee from Modra outside the submitted work. The editorialists reported no competing interests.
Source: Henricks LM et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30686-7.
ESMO 2018: First look at immunotherapy as first-line treatment for HNSCC
for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) will be presented during a presidential symposium at the European Society for Medical Oncology Congress.
The drug is currently approved for second-line treatment of HNSCC. Merck, the maker of the anti–programmed cell death protein therapy, announced in July that the primary endpoint of overall survival as monotherapy in the first-line setting of advanced HNSCC had been met in patients whose tumors expressed programmed death–ligand 1.
More than 800 patients in KEYNOTE-048 were randomized to receive pembrolizumab as monotherapy or in combination with cisplatin or carboplatin and 5-FU, or cetuximab plus cisplatin or carboplatin and 5-FU.
The dual primary endpoints were overall survival and progression-free survival. The secondary endpoints of the study were PFS (at 6 months and 12 months), objective response rate, and time to deterioration in Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, according to the company.
Further details from the interim analysis of KEYNOTE-048 will be presented by Barbara Burtness, MD, of Yale Cancer Center, New Haven, Conn., during Presidential Symposium 3 at ESMO 2018 on Oct. 22 in Munich.
for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) will be presented during a presidential symposium at the European Society for Medical Oncology Congress.
The drug is currently approved for second-line treatment of HNSCC. Merck, the maker of the anti–programmed cell death protein therapy, announced in July that the primary endpoint of overall survival as monotherapy in the first-line setting of advanced HNSCC had been met in patients whose tumors expressed programmed death–ligand 1.
More than 800 patients in KEYNOTE-048 were randomized to receive pembrolizumab as monotherapy or in combination with cisplatin or carboplatin and 5-FU, or cetuximab plus cisplatin or carboplatin and 5-FU.
The dual primary endpoints were overall survival and progression-free survival. The secondary endpoints of the study were PFS (at 6 months and 12 months), objective response rate, and time to deterioration in Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, according to the company.
Further details from the interim analysis of KEYNOTE-048 will be presented by Barbara Burtness, MD, of Yale Cancer Center, New Haven, Conn., during Presidential Symposium 3 at ESMO 2018 on Oct. 22 in Munich.
for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) will be presented during a presidential symposium at the European Society for Medical Oncology Congress.
The drug is currently approved for second-line treatment of HNSCC. Merck, the maker of the anti–programmed cell death protein therapy, announced in July that the primary endpoint of overall survival as monotherapy in the first-line setting of advanced HNSCC had been met in patients whose tumors expressed programmed death–ligand 1.
More than 800 patients in KEYNOTE-048 were randomized to receive pembrolizumab as monotherapy or in combination with cisplatin or carboplatin and 5-FU, or cetuximab plus cisplatin or carboplatin and 5-FU.
The dual primary endpoints were overall survival and progression-free survival. The secondary endpoints of the study were PFS (at 6 months and 12 months), objective response rate, and time to deterioration in Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, according to the company.
Further details from the interim analysis of KEYNOTE-048 will be presented by Barbara Burtness, MD, of Yale Cancer Center, New Haven, Conn., during Presidential Symposium 3 at ESMO 2018 on Oct. 22 in Munich.
Updated analysis from JAVELIN Renal 101 to be presented at ESMO 2018
An updated analysis of interim results for JAVELIN Renal 101 will be presented at a Presidential Symposium during the annual congress of the European Society for Medical Oncology (ESMO 2018), to be held Oct. 19-23 in Munich.
The phase 3 trial compared avelumab (Bavencio) in combination with axitinib (Inlyta) to sunitinib monotherapy as first-line treatment, in patients with advanced renal cell carcinoma (RCC). Interim analysis results announced by the company in a September press release indicated the combination of immunotherapy and a tyrosine kinase inhibitor showed “a statistically significant improvement in progression-free survival by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).”
An updated analysis of progression-free survival and overall response rates will be presented at ESMO 2018 by Robert J. Motzer, MD of Memorial Sloan Kettering Cancer Center, New York.
A phase 1b study (JAVELIN Renal 100), published in Lancet Oncology, found the safety profile of the combination to be similar to either drug alone.
For the phase 3 trial, more than 800 patients with advanced RCC were randomized to first-line treatment with the combination of avelumab (10 mg/kg IV every 2 weeks) plus axitinib (5 mg orally, twice daily) or monotherapy with sunitinib (50 mg orally once daily, 4 weeks on/2 weeks off). The overall survival results will be presented at the Presidential Symposium 2 on Oct. 21.
This article was updated on 10/15/18 to reflect the fact that interim results will be presented.
An updated analysis of interim results for JAVELIN Renal 101 will be presented at a Presidential Symposium during the annual congress of the European Society for Medical Oncology (ESMO 2018), to be held Oct. 19-23 in Munich.
The phase 3 trial compared avelumab (Bavencio) in combination with axitinib (Inlyta) to sunitinib monotherapy as first-line treatment, in patients with advanced renal cell carcinoma (RCC). Interim analysis results announced by the company in a September press release indicated the combination of immunotherapy and a tyrosine kinase inhibitor showed “a statistically significant improvement in progression-free survival by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).”
An updated analysis of progression-free survival and overall response rates will be presented at ESMO 2018 by Robert J. Motzer, MD of Memorial Sloan Kettering Cancer Center, New York.
A phase 1b study (JAVELIN Renal 100), published in Lancet Oncology, found the safety profile of the combination to be similar to either drug alone.
For the phase 3 trial, more than 800 patients with advanced RCC were randomized to first-line treatment with the combination of avelumab (10 mg/kg IV every 2 weeks) plus axitinib (5 mg orally, twice daily) or monotherapy with sunitinib (50 mg orally once daily, 4 weeks on/2 weeks off). The overall survival results will be presented at the Presidential Symposium 2 on Oct. 21.
This article was updated on 10/15/18 to reflect the fact that interim results will be presented.
An updated analysis of interim results for JAVELIN Renal 101 will be presented at a Presidential Symposium during the annual congress of the European Society for Medical Oncology (ESMO 2018), to be held Oct. 19-23 in Munich.
The phase 3 trial compared avelumab (Bavencio) in combination with axitinib (Inlyta) to sunitinib monotherapy as first-line treatment, in patients with advanced renal cell carcinoma (RCC). Interim analysis results announced by the company in a September press release indicated the combination of immunotherapy and a tyrosine kinase inhibitor showed “a statistically significant improvement in progression-free survival by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).”
An updated analysis of progression-free survival and overall response rates will be presented at ESMO 2018 by Robert J. Motzer, MD of Memorial Sloan Kettering Cancer Center, New York.
A phase 1b study (JAVELIN Renal 100), published in Lancet Oncology, found the safety profile of the combination to be similar to either drug alone.
For the phase 3 trial, more than 800 patients with advanced RCC were randomized to first-line treatment with the combination of avelumab (10 mg/kg IV every 2 weeks) plus axitinib (5 mg orally, twice daily) or monotherapy with sunitinib (50 mg orally once daily, 4 weeks on/2 weeks off). The overall survival results will be presented at the Presidential Symposium 2 on Oct. 21.
This article was updated on 10/15/18 to reflect the fact that interim results will be presented.
ESMO 2018 to highlight research on advanced breast cancer
Oncology Practice will have on-site reporters in Munich covering the European Society for Medical Oncology 2018 Congress, held October 19-23.
A total of 2,051 abstracts will be presented, covering the latest in immunotherapy, technologies of the future, biomarkers, basic and translational research, and prevention, according to an ESMO press release.
Results from four studies on advanced breast cancer will be featured in the first presidential symposium:
- LBA1 – Results of IMpassion130: Results from a global, randomized, double-blind, phase 3 study of atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment-naive locally advanced or metastatic triple-negative breast cancer.
- LBA2 – Analyses from PALOMA-3: Overall survival with palbociclib plus fulvestrant in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.
- LBA3 – Results of the phase 3 SOLAR-1 trial: Alpelisib + fulvestrant for advanced breast cancer.
- 283O PR – Results of the phase 3 trial: Chidamide, a subtype-selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor–positive advanced breast cancer.
Additional late-breaking plenary sessions will cover research on alectinib vs. crizotinib for treatment-naive anaplastic lymphoma kinase positive advanced non–small cell lung cancer, avelumab + axitinib vs. sunitinib as first-line treatment of advanced renal cell carcinoma, and a poly ADP-ribose polymerase inhibitor for maintenance therapy in advanced ovarian cancer
.
Oncology Practice will have on-site reporters in Munich covering the European Society for Medical Oncology 2018 Congress, held October 19-23.
A total of 2,051 abstracts will be presented, covering the latest in immunotherapy, technologies of the future, biomarkers, basic and translational research, and prevention, according to an ESMO press release.
Results from four studies on advanced breast cancer will be featured in the first presidential symposium:
- LBA1 – Results of IMpassion130: Results from a global, randomized, double-blind, phase 3 study of atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment-naive locally advanced or metastatic triple-negative breast cancer.
- LBA2 – Analyses from PALOMA-3: Overall survival with palbociclib plus fulvestrant in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.
- LBA3 – Results of the phase 3 SOLAR-1 trial: Alpelisib + fulvestrant for advanced breast cancer.
- 283O PR – Results of the phase 3 trial: Chidamide, a subtype-selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor–positive advanced breast cancer.
Additional late-breaking plenary sessions will cover research on alectinib vs. crizotinib for treatment-naive anaplastic lymphoma kinase positive advanced non–small cell lung cancer, avelumab + axitinib vs. sunitinib as first-line treatment of advanced renal cell carcinoma, and a poly ADP-ribose polymerase inhibitor for maintenance therapy in advanced ovarian cancer
.
Oncology Practice will have on-site reporters in Munich covering the European Society for Medical Oncology 2018 Congress, held October 19-23.
A total of 2,051 abstracts will be presented, covering the latest in immunotherapy, technologies of the future, biomarkers, basic and translational research, and prevention, according to an ESMO press release.
Results from four studies on advanced breast cancer will be featured in the first presidential symposium:
- LBA1 – Results of IMpassion130: Results from a global, randomized, double-blind, phase 3 study of atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment-naive locally advanced or metastatic triple-negative breast cancer.
- LBA2 – Analyses from PALOMA-3: Overall survival with palbociclib plus fulvestrant in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.
- LBA3 – Results of the phase 3 SOLAR-1 trial: Alpelisib + fulvestrant for advanced breast cancer.
- 283O PR – Results of the phase 3 trial: Chidamide, a subtype-selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor–positive advanced breast cancer.
Additional late-breaking plenary sessions will cover research on alectinib vs. crizotinib for treatment-naive anaplastic lymphoma kinase positive advanced non–small cell lung cancer, avelumab + axitinib vs. sunitinib as first-line treatment of advanced renal cell carcinoma, and a poly ADP-ribose polymerase inhibitor for maintenance therapy in advanced ovarian cancer
.