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DLBCL survival improved with novel antibody-drug conjugate
STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.
Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.
More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.
“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.
However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.
Polatuzumab vedotin consists of an antibody targeted against CD79b, an antigenic protein expressed on the surface of normal B cells, as well as DLBCL and follicular lymphoma cells.
Dr. Sehn and her colleagues enrolled 80 patients with DLBCL for whom first-line chemoimmunotherapy had failed and who were ineligible for stem cell transplant due to age and/or comorbidities.
A second cohort included 80 patients with follicular lymphoma. In this group, median PFS with polatuzumab vedotin/BR was 17 months versus 17.3 months for BR alone, and median overall survival had not been reached in either arm at the time of the data cutoff.
In the DLBCL cohort, patients were randomized to receive polatuzumab vedotin 1.8 mg/kg plus bendamustine 90mg/m2 for 2 days and rituximab 375mg/m2) or BR alone for six 21-day cycles.
The complete response rate by PET scan – the primary endpoint – was significantly higher with polatuzmab/BR at 40% versus 15% for BR alone (P = .012). Respective overall response rates were 45% versus 18% (P = .008). Also, median PFS with the polatuzmab/BR therapy was 6.7 months versus 2.0 months for BR alone, translating into a hazard ratio of 0.31 (P less than .0001).
Respective median overall survival was 11.8 versus 4.7 months, translating into a hazard ratio for the polatuzmab/BR combination of 0.35 (P = .0008).
The PET complete response rates were higher with polatuzmab/BR regardless of prior lines of therapy or refractory status, Dr. Sehn noted.
“In terms of the safety, I think importantly in the combination there were no unexpected toxicities, so typical to what we would expect with what’s known with this drug alone,” Dr. Sehn said.
Grade 3 or greater toxicities that were higher with the polatuzmab/BR combination included cytopenias, febrile neutropenia, and infections. The single serious adverse event that had a higher incidence in the polatuzumab/BR arm was febrile neutropenia (DLBCL). In total, 12% of patients in the polatuzumab-containing arm and 11% of patients in the BR-only arm died on study. Many of the deaths were due to disease progression.
Anton Hagenbeek, MD, PhD, from the Academic Medical Center at the University of Amsterdam, the Netherlands, who moderated the briefing but was not involved in the study, said that about 20%-30% of patients with relapsed/refractory DLBCL are positive for the CD33 antigen, the target of brentuximab vedotin (Adcetris), and noted that this agent is also being tested in a phase 2 trial.
Martin Hutchings, MD, PhD, from Rigshospitalet in Copenhagen, the Netherlands, who co-moderated the oral abstract session, commented that “it’s not so often that we see significant overall survival differences in a phase 2 study with 80 patients.”
Based on the results of this trial, polatuzumab has been granted breakthrough therapy designation by the U.S. Food and Drug Administration and a PRIME (priority medicine) designation from the European Medicines Agency.
SOURCE: Sehn LH et al. EHA Congress, Abstract S802.
STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.
Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.
More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.
“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.
However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.
Polatuzumab vedotin consists of an antibody targeted against CD79b, an antigenic protein expressed on the surface of normal B cells, as well as DLBCL and follicular lymphoma cells.
Dr. Sehn and her colleagues enrolled 80 patients with DLBCL for whom first-line chemoimmunotherapy had failed and who were ineligible for stem cell transplant due to age and/or comorbidities.
A second cohort included 80 patients with follicular lymphoma. In this group, median PFS with polatuzumab vedotin/BR was 17 months versus 17.3 months for BR alone, and median overall survival had not been reached in either arm at the time of the data cutoff.
In the DLBCL cohort, patients were randomized to receive polatuzumab vedotin 1.8 mg/kg plus bendamustine 90mg/m2 for 2 days and rituximab 375mg/m2) or BR alone for six 21-day cycles.
The complete response rate by PET scan – the primary endpoint – was significantly higher with polatuzmab/BR at 40% versus 15% for BR alone (P = .012). Respective overall response rates were 45% versus 18% (P = .008). Also, median PFS with the polatuzmab/BR therapy was 6.7 months versus 2.0 months for BR alone, translating into a hazard ratio of 0.31 (P less than .0001).
Respective median overall survival was 11.8 versus 4.7 months, translating into a hazard ratio for the polatuzmab/BR combination of 0.35 (P = .0008).
The PET complete response rates were higher with polatuzmab/BR regardless of prior lines of therapy or refractory status, Dr. Sehn noted.
“In terms of the safety, I think importantly in the combination there were no unexpected toxicities, so typical to what we would expect with what’s known with this drug alone,” Dr. Sehn said.
Grade 3 or greater toxicities that were higher with the polatuzmab/BR combination included cytopenias, febrile neutropenia, and infections. The single serious adverse event that had a higher incidence in the polatuzumab/BR arm was febrile neutropenia (DLBCL). In total, 12% of patients in the polatuzumab-containing arm and 11% of patients in the BR-only arm died on study. Many of the deaths were due to disease progression.
Anton Hagenbeek, MD, PhD, from the Academic Medical Center at the University of Amsterdam, the Netherlands, who moderated the briefing but was not involved in the study, said that about 20%-30% of patients with relapsed/refractory DLBCL are positive for the CD33 antigen, the target of brentuximab vedotin (Adcetris), and noted that this agent is also being tested in a phase 2 trial.
Martin Hutchings, MD, PhD, from Rigshospitalet in Copenhagen, the Netherlands, who co-moderated the oral abstract session, commented that “it’s not so often that we see significant overall survival differences in a phase 2 study with 80 patients.”
Based on the results of this trial, polatuzumab has been granted breakthrough therapy designation by the U.S. Food and Drug Administration and a PRIME (priority medicine) designation from the European Medicines Agency.
SOURCE: Sehn LH et al. EHA Congress, Abstract S802.
STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.
Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.
More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.
“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.
However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.
Polatuzumab vedotin consists of an antibody targeted against CD79b, an antigenic protein expressed on the surface of normal B cells, as well as DLBCL and follicular lymphoma cells.
Dr. Sehn and her colleagues enrolled 80 patients with DLBCL for whom first-line chemoimmunotherapy had failed and who were ineligible for stem cell transplant due to age and/or comorbidities.
A second cohort included 80 patients with follicular lymphoma. In this group, median PFS with polatuzumab vedotin/BR was 17 months versus 17.3 months for BR alone, and median overall survival had not been reached in either arm at the time of the data cutoff.
In the DLBCL cohort, patients were randomized to receive polatuzumab vedotin 1.8 mg/kg plus bendamustine 90mg/m2 for 2 days and rituximab 375mg/m2) or BR alone for six 21-day cycles.
The complete response rate by PET scan – the primary endpoint – was significantly higher with polatuzmab/BR at 40% versus 15% for BR alone (P = .012). Respective overall response rates were 45% versus 18% (P = .008). Also, median PFS with the polatuzmab/BR therapy was 6.7 months versus 2.0 months for BR alone, translating into a hazard ratio of 0.31 (P less than .0001).
Respective median overall survival was 11.8 versus 4.7 months, translating into a hazard ratio for the polatuzmab/BR combination of 0.35 (P = .0008).
The PET complete response rates were higher with polatuzmab/BR regardless of prior lines of therapy or refractory status, Dr. Sehn noted.
“In terms of the safety, I think importantly in the combination there were no unexpected toxicities, so typical to what we would expect with what’s known with this drug alone,” Dr. Sehn said.
Grade 3 or greater toxicities that were higher with the polatuzmab/BR combination included cytopenias, febrile neutropenia, and infections. The single serious adverse event that had a higher incidence in the polatuzumab/BR arm was febrile neutropenia (DLBCL). In total, 12% of patients in the polatuzumab-containing arm and 11% of patients in the BR-only arm died on study. Many of the deaths were due to disease progression.
Anton Hagenbeek, MD, PhD, from the Academic Medical Center at the University of Amsterdam, the Netherlands, who moderated the briefing but was not involved in the study, said that about 20%-30% of patients with relapsed/refractory DLBCL are positive for the CD33 antigen, the target of brentuximab vedotin (Adcetris), and noted that this agent is also being tested in a phase 2 trial.
Martin Hutchings, MD, PhD, from Rigshospitalet in Copenhagen, the Netherlands, who co-moderated the oral abstract session, commented that “it’s not so often that we see significant overall survival differences in a phase 2 study with 80 patients.”
Based on the results of this trial, polatuzumab has been granted breakthrough therapy designation by the U.S. Food and Drug Administration and a PRIME (priority medicine) designation from the European Medicines Agency.
SOURCE: Sehn LH et al. EHA Congress, Abstract S802.
REPORTING FROM THE EHA CONGRESS
Key clinical point:
Major finding: The complete response rate with polatuzumab vedotin plus bendamustine/rituximab (BR) was 40%, compared with 15% for BR alone.
Study details: Randomized controlled phase 2 trial in 80 patients with relapsed/refractory DLBCL.
Disclosures: The study was funded by Hoffman-La Roche. Dr. Sehn reported ties to Roche/Genentech and others.
Source: Sehn LH et al. EHA Congress, Abstract S802.
Everolimus/exemestane improves PFS of ER+/HER2– breast cancer vs. everolimus alone
CHICAGO – For women with estrogen receptor–positive breast cancer resistant to endocrine therapy, the combination of everolimus and exemestane had better efficacy than did everolimus alone, but single-agent capecitabine appeared to offer benefit comparable to that of the combination therapy, results of the BOLERO-6 trial suggest.
Among 309 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of everolimus (Afinitor) and exemestane (Aromasin and generics) was associated with a 26% improvement in progression-free survival (PFS) compared with everolimus alone, reported Guy Jerusalem, MD, PhD, of Liege University, Belgium.
There was also, however, a numerical but not statistically significant difference in PFS favoring capecitabine (Xeloda and generics) “which may be attributed to various baseline characteristics favoring capecitabine, and potential informative censoring,” he said at the annual meeting of the American Society of Clinical Oncology.
“We have noted in BOLERO-6 a better-than-expected outcome in median progression-free survival of capecitabine compared with the previously reported 4.1 to 7.9 months median progression-free survival,” he said.
BOLERO-6, results of which were published online June 3 in JAMA Oncology, was a postmarketing study by the sponsors to fulfill commitments to both the Food and Drug Administration and the European Medicines Agency to estimate the treatment benefit with combined everolimus and exemestane vs. monotherapy with everolimus or capecitabine in patients with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Patients from 83 centers in 18 countries were enrolled in the open label, phase 2 study and randomly assigned to receive oral everolimus 10 mg daily with oral exemestane 25 mg daily, everolimus at the same dose alone, or oral capecitabine 1,250 mg/m2 twice daily for 2 weeks on, 1 week off.
The trial was not powered for statistical comparisons between arms, but was instead designed with the primary objective of estimated investigator-assessed PFS for the combination vs. everolimus alone.
At baseline, more patients assigned to capecitabine vs. everolimus-containing regimens were younger than 65, white, had an Eastern Cooperative Oncology Group status of 0 (fully active), and had bone-only metastases. In addition, fewer patients in the capecitabine arm had three or more metastatic sites, Dr. Jerusalem noted,
For the primary analysis, the median PFS with everolimus/exemestane was 8.4 months, compared with 6.8 months for everolimus alone. The estimated hazard ratio (HR) for PFS with everolimus/exemestane vs. everolimus alone was 0.74 (90% confidence interval [CI], 0.57-0.97)
In contrast, median PFS with capecitabine was 9.6 months, with a nonsignificant hazard ratio of 1.26 for the combination (90% CI, 0.96-1.66).
A stratified multivariate Cox regression model controlling for baseline difference and known prognostic factor yielded an HR for PFS of 1.15 (90% CI, 0.86-1.52) for the combination.
Censoring of patients was more frequent in the capecitabine arm (33% vs. 23% in the combination arm), which included 20% of patients on capecitabine who were censored for starting on a new antineoplastic therapy vs. 9% of patients on everolimus/exemestane.
The median time to treatment failure was 5.8 months with the combination, vs. 4.2 months with everolimus alone (HR, 0.66, 90% CI, 0.52-0.4), and 6.2 months with capecitabine alone (HR, 1.03, 90% CI, 0.81-1.31).
Median overall survival was 23.1 months in the combination arm, 29.3 months in the everolimus arm, and 25.6 months in the capecitabine arm. There were no statistically significant differences in overall survival among the groups.
Grade 3 or greater adverse events were more frequent in the combination vs. everolimus arms, and comparable between the combination and capecitabine arms, Dr. Jerusalem said.
Serious adverse events of any grade were more frequent in the combination arm than in the other two arms, but there were no significant differences in discontinuations due to adverse events
“The results of the present study suggest that mTOR inhibitor and endocrine therapy combinations remain important for aromatase inhibitor–refractory disease. Safety and PFS with everolimus plus exemestane in this study were consistent with BOLERO-2 and are now supported by real-world evidence,” the investigators wrote.
“The take home from the BOLERO-6 trial is that the progression-free survival for the combination of everolimus and exemestane is superior to everolimus alone, and is in line with data from the BOLERO-2 trial, and also the PrE0102 study, demonstrating the consistent activity of mTOR inhibition in combination with endocrine therapy in the aromatase inhibitor resistance setting, and this supports our use of the combination in the endocrine resistant patients,” said Cynthia X. Ma, MD, PhD, of Washington University, St. Louis, the invited discussant.
Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
SOURCE: Jerusalem G et al. ASCO 2018 Abstract 1005
CHICAGO – For women with estrogen receptor–positive breast cancer resistant to endocrine therapy, the combination of everolimus and exemestane had better efficacy than did everolimus alone, but single-agent capecitabine appeared to offer benefit comparable to that of the combination therapy, results of the BOLERO-6 trial suggest.
Among 309 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of everolimus (Afinitor) and exemestane (Aromasin and generics) was associated with a 26% improvement in progression-free survival (PFS) compared with everolimus alone, reported Guy Jerusalem, MD, PhD, of Liege University, Belgium.
There was also, however, a numerical but not statistically significant difference in PFS favoring capecitabine (Xeloda and generics) “which may be attributed to various baseline characteristics favoring capecitabine, and potential informative censoring,” he said at the annual meeting of the American Society of Clinical Oncology.
“We have noted in BOLERO-6 a better-than-expected outcome in median progression-free survival of capecitabine compared with the previously reported 4.1 to 7.9 months median progression-free survival,” he said.
BOLERO-6, results of which were published online June 3 in JAMA Oncology, was a postmarketing study by the sponsors to fulfill commitments to both the Food and Drug Administration and the European Medicines Agency to estimate the treatment benefit with combined everolimus and exemestane vs. monotherapy with everolimus or capecitabine in patients with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Patients from 83 centers in 18 countries were enrolled in the open label, phase 2 study and randomly assigned to receive oral everolimus 10 mg daily with oral exemestane 25 mg daily, everolimus at the same dose alone, or oral capecitabine 1,250 mg/m2 twice daily for 2 weeks on, 1 week off.
The trial was not powered for statistical comparisons between arms, but was instead designed with the primary objective of estimated investigator-assessed PFS for the combination vs. everolimus alone.
At baseline, more patients assigned to capecitabine vs. everolimus-containing regimens were younger than 65, white, had an Eastern Cooperative Oncology Group status of 0 (fully active), and had bone-only metastases. In addition, fewer patients in the capecitabine arm had three or more metastatic sites, Dr. Jerusalem noted,
For the primary analysis, the median PFS with everolimus/exemestane was 8.4 months, compared with 6.8 months for everolimus alone. The estimated hazard ratio (HR) for PFS with everolimus/exemestane vs. everolimus alone was 0.74 (90% confidence interval [CI], 0.57-0.97)
In contrast, median PFS with capecitabine was 9.6 months, with a nonsignificant hazard ratio of 1.26 for the combination (90% CI, 0.96-1.66).
A stratified multivariate Cox regression model controlling for baseline difference and known prognostic factor yielded an HR for PFS of 1.15 (90% CI, 0.86-1.52) for the combination.
Censoring of patients was more frequent in the capecitabine arm (33% vs. 23% in the combination arm), which included 20% of patients on capecitabine who were censored for starting on a new antineoplastic therapy vs. 9% of patients on everolimus/exemestane.
The median time to treatment failure was 5.8 months with the combination, vs. 4.2 months with everolimus alone (HR, 0.66, 90% CI, 0.52-0.4), and 6.2 months with capecitabine alone (HR, 1.03, 90% CI, 0.81-1.31).
Median overall survival was 23.1 months in the combination arm, 29.3 months in the everolimus arm, and 25.6 months in the capecitabine arm. There were no statistically significant differences in overall survival among the groups.
Grade 3 or greater adverse events were more frequent in the combination vs. everolimus arms, and comparable between the combination and capecitabine arms, Dr. Jerusalem said.
Serious adverse events of any grade were more frequent in the combination arm than in the other two arms, but there were no significant differences in discontinuations due to adverse events
“The results of the present study suggest that mTOR inhibitor and endocrine therapy combinations remain important for aromatase inhibitor–refractory disease. Safety and PFS with everolimus plus exemestane in this study were consistent with BOLERO-2 and are now supported by real-world evidence,” the investigators wrote.
“The take home from the BOLERO-6 trial is that the progression-free survival for the combination of everolimus and exemestane is superior to everolimus alone, and is in line with data from the BOLERO-2 trial, and also the PrE0102 study, demonstrating the consistent activity of mTOR inhibition in combination with endocrine therapy in the aromatase inhibitor resistance setting, and this supports our use of the combination in the endocrine resistant patients,” said Cynthia X. Ma, MD, PhD, of Washington University, St. Louis, the invited discussant.
Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
SOURCE: Jerusalem G et al. ASCO 2018 Abstract 1005
CHICAGO – For women with estrogen receptor–positive breast cancer resistant to endocrine therapy, the combination of everolimus and exemestane had better efficacy than did everolimus alone, but single-agent capecitabine appeared to offer benefit comparable to that of the combination therapy, results of the BOLERO-6 trial suggest.
Among 309 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of everolimus (Afinitor) and exemestane (Aromasin and generics) was associated with a 26% improvement in progression-free survival (PFS) compared with everolimus alone, reported Guy Jerusalem, MD, PhD, of Liege University, Belgium.
There was also, however, a numerical but not statistically significant difference in PFS favoring capecitabine (Xeloda and generics) “which may be attributed to various baseline characteristics favoring capecitabine, and potential informative censoring,” he said at the annual meeting of the American Society of Clinical Oncology.
“We have noted in BOLERO-6 a better-than-expected outcome in median progression-free survival of capecitabine compared with the previously reported 4.1 to 7.9 months median progression-free survival,” he said.
BOLERO-6, results of which were published online June 3 in JAMA Oncology, was a postmarketing study by the sponsors to fulfill commitments to both the Food and Drug Administration and the European Medicines Agency to estimate the treatment benefit with combined everolimus and exemestane vs. monotherapy with everolimus or capecitabine in patients with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Patients from 83 centers in 18 countries were enrolled in the open label, phase 2 study and randomly assigned to receive oral everolimus 10 mg daily with oral exemestane 25 mg daily, everolimus at the same dose alone, or oral capecitabine 1,250 mg/m2 twice daily for 2 weeks on, 1 week off.
The trial was not powered for statistical comparisons between arms, but was instead designed with the primary objective of estimated investigator-assessed PFS for the combination vs. everolimus alone.
At baseline, more patients assigned to capecitabine vs. everolimus-containing regimens were younger than 65, white, had an Eastern Cooperative Oncology Group status of 0 (fully active), and had bone-only metastases. In addition, fewer patients in the capecitabine arm had three or more metastatic sites, Dr. Jerusalem noted,
For the primary analysis, the median PFS with everolimus/exemestane was 8.4 months, compared with 6.8 months for everolimus alone. The estimated hazard ratio (HR) for PFS with everolimus/exemestane vs. everolimus alone was 0.74 (90% confidence interval [CI], 0.57-0.97)
In contrast, median PFS with capecitabine was 9.6 months, with a nonsignificant hazard ratio of 1.26 for the combination (90% CI, 0.96-1.66).
A stratified multivariate Cox regression model controlling for baseline difference and known prognostic factor yielded an HR for PFS of 1.15 (90% CI, 0.86-1.52) for the combination.
Censoring of patients was more frequent in the capecitabine arm (33% vs. 23% in the combination arm), which included 20% of patients on capecitabine who were censored for starting on a new antineoplastic therapy vs. 9% of patients on everolimus/exemestane.
The median time to treatment failure was 5.8 months with the combination, vs. 4.2 months with everolimus alone (HR, 0.66, 90% CI, 0.52-0.4), and 6.2 months with capecitabine alone (HR, 1.03, 90% CI, 0.81-1.31).
Median overall survival was 23.1 months in the combination arm, 29.3 months in the everolimus arm, and 25.6 months in the capecitabine arm. There were no statistically significant differences in overall survival among the groups.
Grade 3 or greater adverse events were more frequent in the combination vs. everolimus arms, and comparable between the combination and capecitabine arms, Dr. Jerusalem said.
Serious adverse events of any grade were more frequent in the combination arm than in the other two arms, but there were no significant differences in discontinuations due to adverse events
“The results of the present study suggest that mTOR inhibitor and endocrine therapy combinations remain important for aromatase inhibitor–refractory disease. Safety and PFS with everolimus plus exemestane in this study were consistent with BOLERO-2 and are now supported by real-world evidence,” the investigators wrote.
“The take home from the BOLERO-6 trial is that the progression-free survival for the combination of everolimus and exemestane is superior to everolimus alone, and is in line with data from the BOLERO-2 trial, and also the PrE0102 study, demonstrating the consistent activity of mTOR inhibition in combination with endocrine therapy in the aromatase inhibitor resistance setting, and this supports our use of the combination in the endocrine resistant patients,” said Cynthia X. Ma, MD, PhD, of Washington University, St. Louis, the invited discussant.
Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
SOURCE: Jerusalem G et al. ASCO 2018 Abstract 1005
REPORTING FROM ASCO 2018
Key clinical point: The combination of everolimus and exemestane had better efficacy than did everolimus alone in women with ER+/HER2– breast cancer resistant to endocrine therapy.
Major finding: Median PFS with everolimus/exemestane was 8.4 months vs 6.8 months for everolimus.
Study details: Randomized, open label, phase 2 trial of 309 women with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Disclosures: Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
Source: Jerusalem G et al. ASCO 2018, Abstract 1005.
Avelumab does not add punch to ALK inhibitors for ALK+/– NSCLC
CHICAGO – The combination of the immune checkpoint inhibitor avelumab (Bavencio) and the ALK inhibitor lorlatinib in ALK-positive patients was associated with an acceptable safety profile and good activity – albeit not better than lorlatinib alone – in one arm of the phase 1/2b JAVELIN Lung 101 trial.
In contrast, although preclinical data suggested that the combination of an ALK inhibitor and immune checkpoint inhibitor might have synergistic activity in patients with advanced ALK-negative non–small-cell lung cancer (NSCLC), it didn’t pan out in the second arm of the trial, reported Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston.
In the parallel group trial testing combinations of the programmed death ligand-1 (PD-L1) inhibitor avelumab with either of two tyrosine kinase inhibitors (TKIs) – crizotinib (Xalkori) or lorlatinib – the combination of avelumab and crizotinib had an objective response rate (ORR) of just 16.7% in ALK-negative patients, and 5 of 12 patients in this study arm had dose limiting toxicities (DLTs) due to serious adverse events.
“The most common DLTs were increased transaminases, consistent with the recent report of increased hepatotoxicity with the combination of nivolumab and crizotinib in Checkmate 370. While there were two confirmed partial responses, this efficacy would be expected for avelumab alone. No further development of this combination is planned,” Dr. Shaw said in an oral abstract session at the annual meeting of the American Society of Clinical Oncology.
In contrast, in ALK-positive patients, avelumab/lorlatinib was associated with an ORR of 46.4%, although it’s likely that the responses were attributable to lorlatinib alone, and not its anti-PD-L1 partner, she acknowledged.
Synergism sought
The investigators based the study on two hypotheses: The first was that ALK inhibitors, through their immunomodulatory properties, combined with checkpoint inhibitors, could have synergistic activity against non-ALK-driver NSCLC, hence the combination of avelumab and crizotinib in these patients.
Their second hypothesis was that a combination of an ALK inhibitor and checkpoint inhibitor could lead to enhanced efficacy in patients with previously treated ALK-positive NSCLC. To test this combination, they chose to pair avelumab with lorlatinib, a third-generation ALK-targeting TKI with the ability to penetrate the central nervous system. Dr. Shaw and her colleagues had previously shown in a phase 1 trial that this agent has potent activity against ALK-driven tumors with resistance mutations.
Two groups, two TKIs, one PD-L1 inhibitor
Group A in JAVELIN LUNG 101 included 12 patients with ALK-negative NSCLC, no known ROS1 gene rearrangement, c-MET gene amplification, or c-MET exon 14, skipping who had received at least one prior line of systemic therapy, and no prior checkpoint inhibitor. These patients were treated with avelumab 10 mg/kg over a 1-hour IV infusion every 2 weeks, plus 250 mg oral crizotinib twice daily.
Group B included 28 patients with advanced ALK-positive NSCLC, any number of prior regimens (or none), and no prior checkpoint inhibitor therapy. Patients with asymptomatic untreated brain metastases were eligible for treatment. These patients received avelumab at the same dose and schedule as in group A, plus oral lorlatinib 100 mg once daily.
In both arms, patients were assessed for maximum tolerated dose (MTD) and recommended phase 2 doses, DLTs, safety and tolerability, and antitumor activity.
There were no DLTs among 25 patients evaluable for this assessment in the avelumab/lorlatinib arm. In contrast, five patients had DLTs in the avelumab/crizotinib arm, included four transaminases increases and one case each of febrile neutropenia, hepatitis, QT interval prolongation, and rash.
Adverse events of any grade occurred in all patients in group A and in 27 of 28 patients (96.4%) in group B. Grade 3 or greater adverse events occurred in 58.3% and 53.6% of patients, respectively.
In group A, treatment-related serious adverse events were febrile neutropenia, hepatitis, and rash. In group B, these events included pneumonitis, elevated alanine aminotransferase, delirium, fatal dyspnea (one case), and pericardial effusion.
Antitumor activity
In group A (ALK-negative NSCLC), two patients had a partial response (PR), five had stable disease, and five had progressive disease, for an ORR of 16.7. The median time to response was 1.4 months, and the median duration of response was 4.1 months.
In group B (ALK-positive NSCLC). There was one complete response, 12 PRs, six cases of stable disease, and seven of progressive disease. Two patients in this arm were not evaluable for response at the time of the data cutoff in October 2017. The ORR in this arm was 46.4%, median time to response was 1.9 months, and the median duration of response was 7.4 months. Dr. Shaw cautioned, however, that the 95% confidence interval for duration of response in this group was wide (3.7 months to not estimable), because the data were not yet mature and the number of patients was small.
“Longer follow-up will be important to establish the true durability of these responses and to better assess the potential benefit of combined avelumab and lorlatinib in ALK-positive lung cancer,” Dr. Shaw said.
But invited discussant Leora Horn, MD, MSc, of Vanderbilt University Medical Center in Nashville, Tenn., cast doubt on the ALK inhibitor/checkpoint inhibitor combination compared with targeted therapy alone.
“We were hoping to see that combination therapy with ALK tyrosine kinase inhibitors and immune checkpoint inhibitors are superior to therapy with an ALK tyrosine kinase inhibitor alone, that combination therapy is safe with a manageable toxicity profile, and lastly, that combination therapy with an ALK TKI and immune checkpoint inhibitor is superior to immune checkpoint inhibitor alone in ALK wild type patients,” she said.
She noted that previous phase 1 data with lorlatinib monotherapy in NSCLC showed an ORR of 46%, compared with 46.4% seen with the addition of avelumab to lorlatinib.
“So where do we go from here? We’ve seen that combination therapy with ALK tyrosine kinase inhibitors and immune checkpoint inhibitors are not the optimal therapeutic strategy in ALK-positive non–small-cell lung cancer. It is difficult to improve on a 70% response rate [with TKIs]. The progression-free survival, which is more important, was also not improved,” she said.
The mechanisms of additive toxicities between TKIs and checkpoints are not well understood, and she suggested that “further studies with biopsies exploring the tumor microenvironment in ALK or other driver-positive non–small-cell lung cancer prior to and after therapy with a TKI may help us better define the optimal combination strategy going forward.”
In a panel discussion following her talk, Dr. Shaw was asked what proportion of the responses her team saw could be attributed to lorlatinib rather than avelumab.
“As we showed, both the response rates and the duration of response were actually pretty similar to what was seen in our previous phase 1/2 study of lorlatinib alone. So one could say that perhaps all of the response that was seen with lorlatinib/avelumab was due to the lorlatinib,” she replied.
She added that several patients have ongoing responses, and that longer follow-up may reveal a benefit for the combination in terms of duration of response.
SOURCE: Shaw AT et al. ASCO 2018, Abstract 9008.
CHICAGO – The combination of the immune checkpoint inhibitor avelumab (Bavencio) and the ALK inhibitor lorlatinib in ALK-positive patients was associated with an acceptable safety profile and good activity – albeit not better than lorlatinib alone – in one arm of the phase 1/2b JAVELIN Lung 101 trial.
In contrast, although preclinical data suggested that the combination of an ALK inhibitor and immune checkpoint inhibitor might have synergistic activity in patients with advanced ALK-negative non–small-cell lung cancer (NSCLC), it didn’t pan out in the second arm of the trial, reported Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston.
In the parallel group trial testing combinations of the programmed death ligand-1 (PD-L1) inhibitor avelumab with either of two tyrosine kinase inhibitors (TKIs) – crizotinib (Xalkori) or lorlatinib – the combination of avelumab and crizotinib had an objective response rate (ORR) of just 16.7% in ALK-negative patients, and 5 of 12 patients in this study arm had dose limiting toxicities (DLTs) due to serious adverse events.
“The most common DLTs were increased transaminases, consistent with the recent report of increased hepatotoxicity with the combination of nivolumab and crizotinib in Checkmate 370. While there were two confirmed partial responses, this efficacy would be expected for avelumab alone. No further development of this combination is planned,” Dr. Shaw said in an oral abstract session at the annual meeting of the American Society of Clinical Oncology.
In contrast, in ALK-positive patients, avelumab/lorlatinib was associated with an ORR of 46.4%, although it’s likely that the responses were attributable to lorlatinib alone, and not its anti-PD-L1 partner, she acknowledged.
Synergism sought
The investigators based the study on two hypotheses: The first was that ALK inhibitors, through their immunomodulatory properties, combined with checkpoint inhibitors, could have synergistic activity against non-ALK-driver NSCLC, hence the combination of avelumab and crizotinib in these patients.
Their second hypothesis was that a combination of an ALK inhibitor and checkpoint inhibitor could lead to enhanced efficacy in patients with previously treated ALK-positive NSCLC. To test this combination, they chose to pair avelumab with lorlatinib, a third-generation ALK-targeting TKI with the ability to penetrate the central nervous system. Dr. Shaw and her colleagues had previously shown in a phase 1 trial that this agent has potent activity against ALK-driven tumors with resistance mutations.
Two groups, two TKIs, one PD-L1 inhibitor
Group A in JAVELIN LUNG 101 included 12 patients with ALK-negative NSCLC, no known ROS1 gene rearrangement, c-MET gene amplification, or c-MET exon 14, skipping who had received at least one prior line of systemic therapy, and no prior checkpoint inhibitor. These patients were treated with avelumab 10 mg/kg over a 1-hour IV infusion every 2 weeks, plus 250 mg oral crizotinib twice daily.
Group B included 28 patients with advanced ALK-positive NSCLC, any number of prior regimens (or none), and no prior checkpoint inhibitor therapy. Patients with asymptomatic untreated brain metastases were eligible for treatment. These patients received avelumab at the same dose and schedule as in group A, plus oral lorlatinib 100 mg once daily.
In both arms, patients were assessed for maximum tolerated dose (MTD) and recommended phase 2 doses, DLTs, safety and tolerability, and antitumor activity.
There were no DLTs among 25 patients evaluable for this assessment in the avelumab/lorlatinib arm. In contrast, five patients had DLTs in the avelumab/crizotinib arm, included four transaminases increases and one case each of febrile neutropenia, hepatitis, QT interval prolongation, and rash.
Adverse events of any grade occurred in all patients in group A and in 27 of 28 patients (96.4%) in group B. Grade 3 or greater adverse events occurred in 58.3% and 53.6% of patients, respectively.
In group A, treatment-related serious adverse events were febrile neutropenia, hepatitis, and rash. In group B, these events included pneumonitis, elevated alanine aminotransferase, delirium, fatal dyspnea (one case), and pericardial effusion.
Antitumor activity
In group A (ALK-negative NSCLC), two patients had a partial response (PR), five had stable disease, and five had progressive disease, for an ORR of 16.7. The median time to response was 1.4 months, and the median duration of response was 4.1 months.
In group B (ALK-positive NSCLC). There was one complete response, 12 PRs, six cases of stable disease, and seven of progressive disease. Two patients in this arm were not evaluable for response at the time of the data cutoff in October 2017. The ORR in this arm was 46.4%, median time to response was 1.9 months, and the median duration of response was 7.4 months. Dr. Shaw cautioned, however, that the 95% confidence interval for duration of response in this group was wide (3.7 months to not estimable), because the data were not yet mature and the number of patients was small.
“Longer follow-up will be important to establish the true durability of these responses and to better assess the potential benefit of combined avelumab and lorlatinib in ALK-positive lung cancer,” Dr. Shaw said.
But invited discussant Leora Horn, MD, MSc, of Vanderbilt University Medical Center in Nashville, Tenn., cast doubt on the ALK inhibitor/checkpoint inhibitor combination compared with targeted therapy alone.
“We were hoping to see that combination therapy with ALK tyrosine kinase inhibitors and immune checkpoint inhibitors are superior to therapy with an ALK tyrosine kinase inhibitor alone, that combination therapy is safe with a manageable toxicity profile, and lastly, that combination therapy with an ALK TKI and immune checkpoint inhibitor is superior to immune checkpoint inhibitor alone in ALK wild type patients,” she said.
She noted that previous phase 1 data with lorlatinib monotherapy in NSCLC showed an ORR of 46%, compared with 46.4% seen with the addition of avelumab to lorlatinib.
“So where do we go from here? We’ve seen that combination therapy with ALK tyrosine kinase inhibitors and immune checkpoint inhibitors are not the optimal therapeutic strategy in ALK-positive non–small-cell lung cancer. It is difficult to improve on a 70% response rate [with TKIs]. The progression-free survival, which is more important, was also not improved,” she said.
The mechanisms of additive toxicities between TKIs and checkpoints are not well understood, and she suggested that “further studies with biopsies exploring the tumor microenvironment in ALK or other driver-positive non–small-cell lung cancer prior to and after therapy with a TKI may help us better define the optimal combination strategy going forward.”
In a panel discussion following her talk, Dr. Shaw was asked what proportion of the responses her team saw could be attributed to lorlatinib rather than avelumab.
“As we showed, both the response rates and the duration of response were actually pretty similar to what was seen in our previous phase 1/2 study of lorlatinib alone. So one could say that perhaps all of the response that was seen with lorlatinib/avelumab was due to the lorlatinib,” she replied.
She added that several patients have ongoing responses, and that longer follow-up may reveal a benefit for the combination in terms of duration of response.
SOURCE: Shaw AT et al. ASCO 2018, Abstract 9008.
CHICAGO – The combination of the immune checkpoint inhibitor avelumab (Bavencio) and the ALK inhibitor lorlatinib in ALK-positive patients was associated with an acceptable safety profile and good activity – albeit not better than lorlatinib alone – in one arm of the phase 1/2b JAVELIN Lung 101 trial.
In contrast, although preclinical data suggested that the combination of an ALK inhibitor and immune checkpoint inhibitor might have synergistic activity in patients with advanced ALK-negative non–small-cell lung cancer (NSCLC), it didn’t pan out in the second arm of the trial, reported Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston.
In the parallel group trial testing combinations of the programmed death ligand-1 (PD-L1) inhibitor avelumab with either of two tyrosine kinase inhibitors (TKIs) – crizotinib (Xalkori) or lorlatinib – the combination of avelumab and crizotinib had an objective response rate (ORR) of just 16.7% in ALK-negative patients, and 5 of 12 patients in this study arm had dose limiting toxicities (DLTs) due to serious adverse events.
“The most common DLTs were increased transaminases, consistent with the recent report of increased hepatotoxicity with the combination of nivolumab and crizotinib in Checkmate 370. While there were two confirmed partial responses, this efficacy would be expected for avelumab alone. No further development of this combination is planned,” Dr. Shaw said in an oral abstract session at the annual meeting of the American Society of Clinical Oncology.
In contrast, in ALK-positive patients, avelumab/lorlatinib was associated with an ORR of 46.4%, although it’s likely that the responses were attributable to lorlatinib alone, and not its anti-PD-L1 partner, she acknowledged.
Synergism sought
The investigators based the study on two hypotheses: The first was that ALK inhibitors, through their immunomodulatory properties, combined with checkpoint inhibitors, could have synergistic activity against non-ALK-driver NSCLC, hence the combination of avelumab and crizotinib in these patients.
Their second hypothesis was that a combination of an ALK inhibitor and checkpoint inhibitor could lead to enhanced efficacy in patients with previously treated ALK-positive NSCLC. To test this combination, they chose to pair avelumab with lorlatinib, a third-generation ALK-targeting TKI with the ability to penetrate the central nervous system. Dr. Shaw and her colleagues had previously shown in a phase 1 trial that this agent has potent activity against ALK-driven tumors with resistance mutations.
Two groups, two TKIs, one PD-L1 inhibitor
Group A in JAVELIN LUNG 101 included 12 patients with ALK-negative NSCLC, no known ROS1 gene rearrangement, c-MET gene amplification, or c-MET exon 14, skipping who had received at least one prior line of systemic therapy, and no prior checkpoint inhibitor. These patients were treated with avelumab 10 mg/kg over a 1-hour IV infusion every 2 weeks, plus 250 mg oral crizotinib twice daily.
Group B included 28 patients with advanced ALK-positive NSCLC, any number of prior regimens (or none), and no prior checkpoint inhibitor therapy. Patients with asymptomatic untreated brain metastases were eligible for treatment. These patients received avelumab at the same dose and schedule as in group A, plus oral lorlatinib 100 mg once daily.
In both arms, patients were assessed for maximum tolerated dose (MTD) and recommended phase 2 doses, DLTs, safety and tolerability, and antitumor activity.
There were no DLTs among 25 patients evaluable for this assessment in the avelumab/lorlatinib arm. In contrast, five patients had DLTs in the avelumab/crizotinib arm, included four transaminases increases and one case each of febrile neutropenia, hepatitis, QT interval prolongation, and rash.
Adverse events of any grade occurred in all patients in group A and in 27 of 28 patients (96.4%) in group B. Grade 3 or greater adverse events occurred in 58.3% and 53.6% of patients, respectively.
In group A, treatment-related serious adverse events were febrile neutropenia, hepatitis, and rash. In group B, these events included pneumonitis, elevated alanine aminotransferase, delirium, fatal dyspnea (one case), and pericardial effusion.
Antitumor activity
In group A (ALK-negative NSCLC), two patients had a partial response (PR), five had stable disease, and five had progressive disease, for an ORR of 16.7. The median time to response was 1.4 months, and the median duration of response was 4.1 months.
In group B (ALK-positive NSCLC). There was one complete response, 12 PRs, six cases of stable disease, and seven of progressive disease. Two patients in this arm were not evaluable for response at the time of the data cutoff in October 2017. The ORR in this arm was 46.4%, median time to response was 1.9 months, and the median duration of response was 7.4 months. Dr. Shaw cautioned, however, that the 95% confidence interval for duration of response in this group was wide (3.7 months to not estimable), because the data were not yet mature and the number of patients was small.
“Longer follow-up will be important to establish the true durability of these responses and to better assess the potential benefit of combined avelumab and lorlatinib in ALK-positive lung cancer,” Dr. Shaw said.
But invited discussant Leora Horn, MD, MSc, of Vanderbilt University Medical Center in Nashville, Tenn., cast doubt on the ALK inhibitor/checkpoint inhibitor combination compared with targeted therapy alone.
“We were hoping to see that combination therapy with ALK tyrosine kinase inhibitors and immune checkpoint inhibitors are superior to therapy with an ALK tyrosine kinase inhibitor alone, that combination therapy is safe with a manageable toxicity profile, and lastly, that combination therapy with an ALK TKI and immune checkpoint inhibitor is superior to immune checkpoint inhibitor alone in ALK wild type patients,” she said.
She noted that previous phase 1 data with lorlatinib monotherapy in NSCLC showed an ORR of 46%, compared with 46.4% seen with the addition of avelumab to lorlatinib.
“So where do we go from here? We’ve seen that combination therapy with ALK tyrosine kinase inhibitors and immune checkpoint inhibitors are not the optimal therapeutic strategy in ALK-positive non–small-cell lung cancer. It is difficult to improve on a 70% response rate [with TKIs]. The progression-free survival, which is more important, was also not improved,” she said.
The mechanisms of additive toxicities between TKIs and checkpoints are not well understood, and she suggested that “further studies with biopsies exploring the tumor microenvironment in ALK or other driver-positive non–small-cell lung cancer prior to and after therapy with a TKI may help us better define the optimal combination strategy going forward.”
In a panel discussion following her talk, Dr. Shaw was asked what proportion of the responses her team saw could be attributed to lorlatinib rather than avelumab.
“As we showed, both the response rates and the duration of response were actually pretty similar to what was seen in our previous phase 1/2 study of lorlatinib alone. So one could say that perhaps all of the response that was seen with lorlatinib/avelumab was due to the lorlatinib,” she replied.
She added that several patients have ongoing responses, and that longer follow-up may reveal a benefit for the combination in terms of duration of response.
SOURCE: Shaw AT et al. ASCO 2018, Abstract 9008.
REPORTING FROM ASCO 2018
Key clinical point: Adding an anti-PD-L1 checkpoint inhibitor to an ALK inhibitor did not add efficacy in patients with either ALK-negative or ALK-positive non–small-cell lung cancer.
Major finding: The ORR in patients treated with avelumab/lorlatinib was 46.4%, the same as ORR with lorlatinib alone.
Study details: Phase 1/2 trial of avelumab/crizotinib in 12 patients with ALK-negative NSCLC, and avelumab/lorlatinib in 28 patients with ALK-positive NSCLC.
Disclosures: Pfizer sponsored the trial. Dr. Shaw disclosed consultancy/advisory board membership, researching funding, and honoraria from Pfizer and other companies. Dr. Horn has previously disclosed serving as a consultant to AbbVie, BMS, Genentech, Merck, and AstraZeneca.
Source: Shaw AT et al. ASCO 2018, Abstract 9008.
Geriatric assessments improve oncologist-patient communications
CHICAGO – Elderly cancer patients have better communication with their oncologists and report greater satisfaction with their care when the oncologists are provided with geriatric assessment summaries prior to the patient visit.
Although “satisfaction” can be subjective, the conclusion about the benefit of previsit geriatric assessments is objective, reported Supriya Gupta Mohile, MD, of the University of Rochester, New York.
“Physicians often don’t know patients’ and caregivers’ age-related concerns, such as concerns about memory or concerns about falling. Many patients and caregivers do not ask about age-related concerns, because of their unclear understanding of the relevance of those issues to an oncology clinical encounter,” she added.
The aim of the researchers was to see whether communication between physicians and their elderly patients could be improved, and patient support needs addressed, with the aid of the Geriatric Assessment (GA), a multidisciplinary diagnostic and treatment instrument.
The GA evaluates patients in the domains of functional status, objective physical performance, comorbidities, cognition, nutritional status, psychological status, and social support, and identifies vulnerabilities that could be addressed by specific interventions.
For example, patients with suboptimal physical performance may trigger recommendations for fall prevention and a review of medications that could increase fall risk. For patients with decrements in functional status, recommendations may include physical therapy, safety evaluation, and/or vision assessment.
Each domain independently predicts morbidity and/or mortality in older patients.
The investigators enrolled 31 oncology practices in the National Cancer Institute’s Community Oncology Research Program that were treating patients aged 70 or older with advanced solid tumors or lymphoma. Patients who were enrolled had at least one impaired GA domain. In all, 542 patients across the sites were enrolled.
All patients in each arm completed the GA.
Randomization was by practice, with practices in arm 1 randomized to receive GA intervention results. Oncologists in this trial arm were provided with a GA summary and list of recommended GA-guided interventions.
Practices in arm 2 (controls) did not receive summaries or lists of recommendations, but oncologists were notified if patients had clinically significant depression or cognitive impairment.
In the intervention group, patients completed all assessments within 30 minutes, and less than 10 minutes of practice staff time was required for administration of objective tests.
The investigators made audio recordings and transcripts of clinic visits after GA in both arms, with two blinded coders evaluating quality of communication and plans for follow-up interventions. Patients were surveyed by telephone about their satisfaction, via the Health Care Climate Questionnaire (HCCQ) and the same instrument modified for age-related concerns (HCCQ-age).
“We found that patients enrolled in the study had a high prevalence of impairments of Geriatric Assessment domains, ranging from over 90% for physical performance, to 25% for psychological status, mainly depression. Of note, more than 30% of patients ... screened positive for cognitive impairment.” Dr. Mohile said.
For the coprimary endpoint of communication about age-related concerns, the mean number of discussions was 7.74 in the GA arm, compared with 4.24 in the control arm, a difference of 3.5 (P less than .0001).
Arm 1 was rated as having more discussions with higher-quality communications (mean 4.42 vs. 2.47, P less than .0001), and had more discussions leading to an intervention (3.08 vs. 1.15, P less than .0001).
Patients in arm 1 consistently rated their satisfaction with communication (the other coprimary endpoint) higher than did patients in arm 2, at both baseline, 4-6 weeks after the visit, and 3 months after the visit.
“This is a very important study that I think is likely to have a direct impact on the care of older patients with cancer,” ASCO expert Joshua A. Jones, MD, of the University of Pennsylvania, Philadelphia, said at the meeting.
“This study shows in a randomized fashion that we can, with a simple intervention, improve communication about what’s really important to older patients with cancer,” he said. “We have interventions, things like physical therapy, things like counseling, supports that can be provided to patients and families as they are thinking through treatment decisions, helping us to provide the most appropriate care for these individuals.”
SOURCE: Mohile SG et al. ASCO 2018, abstract LBA10003.
CHICAGO – Elderly cancer patients have better communication with their oncologists and report greater satisfaction with their care when the oncologists are provided with geriatric assessment summaries prior to the patient visit.
Although “satisfaction” can be subjective, the conclusion about the benefit of previsit geriatric assessments is objective, reported Supriya Gupta Mohile, MD, of the University of Rochester, New York.
“Physicians often don’t know patients’ and caregivers’ age-related concerns, such as concerns about memory or concerns about falling. Many patients and caregivers do not ask about age-related concerns, because of their unclear understanding of the relevance of those issues to an oncology clinical encounter,” she added.
The aim of the researchers was to see whether communication between physicians and their elderly patients could be improved, and patient support needs addressed, with the aid of the Geriatric Assessment (GA), a multidisciplinary diagnostic and treatment instrument.
The GA evaluates patients in the domains of functional status, objective physical performance, comorbidities, cognition, nutritional status, psychological status, and social support, and identifies vulnerabilities that could be addressed by specific interventions.
For example, patients with suboptimal physical performance may trigger recommendations for fall prevention and a review of medications that could increase fall risk. For patients with decrements in functional status, recommendations may include physical therapy, safety evaluation, and/or vision assessment.
Each domain independently predicts morbidity and/or mortality in older patients.
The investigators enrolled 31 oncology practices in the National Cancer Institute’s Community Oncology Research Program that were treating patients aged 70 or older with advanced solid tumors or lymphoma. Patients who were enrolled had at least one impaired GA domain. In all, 542 patients across the sites were enrolled.
All patients in each arm completed the GA.
Randomization was by practice, with practices in arm 1 randomized to receive GA intervention results. Oncologists in this trial arm were provided with a GA summary and list of recommended GA-guided interventions.
Practices in arm 2 (controls) did not receive summaries or lists of recommendations, but oncologists were notified if patients had clinically significant depression or cognitive impairment.
In the intervention group, patients completed all assessments within 30 minutes, and less than 10 minutes of practice staff time was required for administration of objective tests.
The investigators made audio recordings and transcripts of clinic visits after GA in both arms, with two blinded coders evaluating quality of communication and plans for follow-up interventions. Patients were surveyed by telephone about their satisfaction, via the Health Care Climate Questionnaire (HCCQ) and the same instrument modified for age-related concerns (HCCQ-age).
“We found that patients enrolled in the study had a high prevalence of impairments of Geriatric Assessment domains, ranging from over 90% for physical performance, to 25% for psychological status, mainly depression. Of note, more than 30% of patients ... screened positive for cognitive impairment.” Dr. Mohile said.
For the coprimary endpoint of communication about age-related concerns, the mean number of discussions was 7.74 in the GA arm, compared with 4.24 in the control arm, a difference of 3.5 (P less than .0001).
Arm 1 was rated as having more discussions with higher-quality communications (mean 4.42 vs. 2.47, P less than .0001), and had more discussions leading to an intervention (3.08 vs. 1.15, P less than .0001).
Patients in arm 1 consistently rated their satisfaction with communication (the other coprimary endpoint) higher than did patients in arm 2, at both baseline, 4-6 weeks after the visit, and 3 months after the visit.
“This is a very important study that I think is likely to have a direct impact on the care of older patients with cancer,” ASCO expert Joshua A. Jones, MD, of the University of Pennsylvania, Philadelphia, said at the meeting.
“This study shows in a randomized fashion that we can, with a simple intervention, improve communication about what’s really important to older patients with cancer,” he said. “We have interventions, things like physical therapy, things like counseling, supports that can be provided to patients and families as they are thinking through treatment decisions, helping us to provide the most appropriate care for these individuals.”
SOURCE: Mohile SG et al. ASCO 2018, abstract LBA10003.
CHICAGO – Elderly cancer patients have better communication with their oncologists and report greater satisfaction with their care when the oncologists are provided with geriatric assessment summaries prior to the patient visit.
Although “satisfaction” can be subjective, the conclusion about the benefit of previsit geriatric assessments is objective, reported Supriya Gupta Mohile, MD, of the University of Rochester, New York.
“Physicians often don’t know patients’ and caregivers’ age-related concerns, such as concerns about memory or concerns about falling. Many patients and caregivers do not ask about age-related concerns, because of their unclear understanding of the relevance of those issues to an oncology clinical encounter,” she added.
The aim of the researchers was to see whether communication between physicians and their elderly patients could be improved, and patient support needs addressed, with the aid of the Geriatric Assessment (GA), a multidisciplinary diagnostic and treatment instrument.
The GA evaluates patients in the domains of functional status, objective physical performance, comorbidities, cognition, nutritional status, psychological status, and social support, and identifies vulnerabilities that could be addressed by specific interventions.
For example, patients with suboptimal physical performance may trigger recommendations for fall prevention and a review of medications that could increase fall risk. For patients with decrements in functional status, recommendations may include physical therapy, safety evaluation, and/or vision assessment.
Each domain independently predicts morbidity and/or mortality in older patients.
The investigators enrolled 31 oncology practices in the National Cancer Institute’s Community Oncology Research Program that were treating patients aged 70 or older with advanced solid tumors or lymphoma. Patients who were enrolled had at least one impaired GA domain. In all, 542 patients across the sites were enrolled.
All patients in each arm completed the GA.
Randomization was by practice, with practices in arm 1 randomized to receive GA intervention results. Oncologists in this trial arm were provided with a GA summary and list of recommended GA-guided interventions.
Practices in arm 2 (controls) did not receive summaries or lists of recommendations, but oncologists were notified if patients had clinically significant depression or cognitive impairment.
In the intervention group, patients completed all assessments within 30 minutes, and less than 10 minutes of practice staff time was required for administration of objective tests.
The investigators made audio recordings and transcripts of clinic visits after GA in both arms, with two blinded coders evaluating quality of communication and plans for follow-up interventions. Patients were surveyed by telephone about their satisfaction, via the Health Care Climate Questionnaire (HCCQ) and the same instrument modified for age-related concerns (HCCQ-age).
“We found that patients enrolled in the study had a high prevalence of impairments of Geriatric Assessment domains, ranging from over 90% for physical performance, to 25% for psychological status, mainly depression. Of note, more than 30% of patients ... screened positive for cognitive impairment.” Dr. Mohile said.
For the coprimary endpoint of communication about age-related concerns, the mean number of discussions was 7.74 in the GA arm, compared with 4.24 in the control arm, a difference of 3.5 (P less than .0001).
Arm 1 was rated as having more discussions with higher-quality communications (mean 4.42 vs. 2.47, P less than .0001), and had more discussions leading to an intervention (3.08 vs. 1.15, P less than .0001).
Patients in arm 1 consistently rated their satisfaction with communication (the other coprimary endpoint) higher than did patients in arm 2, at both baseline, 4-6 weeks after the visit, and 3 months after the visit.
“This is a very important study that I think is likely to have a direct impact on the care of older patients with cancer,” ASCO expert Joshua A. Jones, MD, of the University of Pennsylvania, Philadelphia, said at the meeting.
“This study shows in a randomized fashion that we can, with a simple intervention, improve communication about what’s really important to older patients with cancer,” he said. “We have interventions, things like physical therapy, things like counseling, supports that can be provided to patients and families as they are thinking through treatment decisions, helping us to provide the most appropriate care for these individuals.”
SOURCE: Mohile SG et al. ASCO 2018, abstract LBA10003.
REPORTING FROM ASCO 2018
Key clinical point: Geriatric cancer patients may have age-related concerns that they don’t bring up during an oncology visit, but that could affect their care.
Major finding: Patients whose oncologists received geriatric assessment results had significantly more and higher quality discussions of age-related concerns, and were significantly more satisfied with their communications at follow-up.
Study details: Cluster randomized controlled trial comprising 542 patients aged 70 and older from 31 community oncology sites.
Disclosures: The National Cancer Institute funded the study. Dr. Mohile disclosed a consulting/advisory role with Seattle Genetics. Dr. Jones reported no conflicts of interest relevant to the study.
Source: Mohile SG et al. ASCO 2018, abstract LBA10003.
Frontline immunotherapy boosts survival in NSCLC patients
CHICAGO – Pembrolizumab (Keytruda) as first-line treatment of advanced non–small-cell lung cancer (NSCLC) offered longer overall survival with better tolerability compared with chemotherapy, results of the Keynote-042 phase 3 randomized trial show.
Among 1,274 patients with advanced, previously untreated NSCLC with expression of the PD-L1 on 1% or more of tumor cells, median overall survival after a median follow-up of 12.8 months was 16.7 months for patients treated with pembrolizumab monotherapy, compared with 12.1 months for patients treated with either paclitaxel or pemetrexed plus carboplatin, reported lead author Gilberto Lopes, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami.
For all three PD-L1 expression groups, the median duration of response was 20.2 months, compared with 10.8-8.3 months for patients in the chemotherapy arm.
“These are responses that are unlike anything that we have seen with chemotherapy in the past for non–small-cell lung cancer,” Dr. Lopes said at a briefing prior to his presentation of the data in a plenary session.
“In addition to that, and probably more importantly, patients had fewer adverse events [with pembrolizumab]. Overall, about 60% had any treatment-related adverse event with pembrolizumab, vs. 90% with chemotherapy,” he added.
‘A true milestone’
ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, said at the briefing that “this study represents a true milestone for the field, because now, for the first time, we can say that among non–small-cell lung cancer patients receiving first-line therapy, the vast majority can receive immunotherapy with pembrolizumab instead of chemotherapy.”
He noted that an earlier study, Keynote-024, showed that pembrolizumab significantly improved progression-free survival in patients with tumors expressing PD-L1 on at least 50% of cells compared with standard platinum-based chemotherapy (10.3 vs. 6 months).
The Keynote-042 investigators enrolled 1,274 patients with locally advanced or metastatic NSCLC, and randomly assigned them to receive either a maximum of 35 cycles of pembrolizumab 200 mg every 3 weeks, or the investigators’ choice of not more than 6 cycles of either paclitaxel/carboplatin or pemetrexed/carboplatin, with optional pemetrexed maintenance for patients with nonsquamous histologies only.
The randomization was stratified by region (Asia vs. non–East Asia), Eastern Cooperative Oncology Group performance status 0 or 1, squamous vs. nonsquamous histology, and PD-L1 expression, or TPS (tumor proportion score) greater than 50% vs. 1%-49%.
As noted before, the primary endpoint of overall survival among all patients with a TPS of 1% or greater was met, with respective median overall survival in the pembrolizumab vs. chemotherapy groups of 16.7 vs. 12.1 months, translating into a hazard ratio favoring pembrolizumab of 0.81 (P = .0018). Respective hazard ratios for the TPS 20% or greater and TPS 50% or greater groups were 0.77 (P = .0020), and 0.69 (P = .0003).
At 12.8 months of median follow-up, 13% of patients assigned to pembrolizumab were still on the drug, and 4.3% of patients were receiving maintenance pemetrexed.
Treatment-related adverse events of any grade occurred in 399 of 636 patients assigned to pembrolizumab (62.7%), vs. 553 of 615 patients assigned to chemotherapy (89.9%).
Grade 3 or greater events occurred in 17.8% vs. 41% of patients, respectively, There were 13 deaths related to therapy in the pembrolizumab arm (2.0%), and 14 in the chemotherapy arm (2.3%).
Adverse events leading to discontinuation were similar between the groups, at 9% and 9.4%, respectively.
There were more immune-mediated adverse events in the pembrolizumab arm (27.8% vs. 7.2%), and of these, grade 3 or greater events occurred in 8% vs. 1.5% of patients, respectively.
There was one immune-mediated death, from pneumonitis, in the immunotherapy arm; there were no deaths related to immune-mediated side effects in the chemotherapy arm.
“I really view this as a ‘double whammy’ for patients,” Dr. Heymach said at the briefing. “Often advances in survival for our lung cancer patients come at the cost of significant toxicities. Here, by contrast, not only are patients living longer and having a much higher likelihood of prolonged survival in years, often instead of months, but they’re also receiving a treatment that has substantially less toxicity across virtually all measures, and this really impacts the day-to-day life of these patients.”
Leena Gandhi, MD, PhD, of the Perlmutter Cancer Center at New York University, the invited discussant at the plenary, agreed that pembrolizumab improves survival, compared with chemotherapy patients with PD-L1 expression levels greater than 1%, but noted that most of the benefit – as also seen in Keynote-024 – was in those patients whose tumors had high levels of PD-L1 expression.
She emphasized that although PD-L1 is an imperfect biomarker, it should still be used to help select patients for therapy, and may be complementary with tumor mutational burden for more precise treatment selection.
“What we know, and what this study adds to, is that PD-L1 really does define a patient population that could receive benefit from pembrolizumab over chemotherapy. Patients with low or no PD-L1 expression likely should get some type of combination therapy,” she said.
“I do think this study extends what we’ve seen from other recent studies, which is that chemotherapy alone is no longer a first-line standard of care in non–small-cell lung cancer,” she added.
Merck funded the study. Dr. Lopes disclosed institutional research funding from Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Dr. Heymach disclosed stock/ownership in Bio-Tree and Cardinal Spine, a consulting or advisory role for Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, and Synta, and institutional research funding from AstraZeneca. Dr. Gandhi reported having no relevant disclosures.
SOURCE: Lobes G et al. ASCO 2018, abstract LBA4.
CHICAGO – Pembrolizumab (Keytruda) as first-line treatment of advanced non–small-cell lung cancer (NSCLC) offered longer overall survival with better tolerability compared with chemotherapy, results of the Keynote-042 phase 3 randomized trial show.
Among 1,274 patients with advanced, previously untreated NSCLC with expression of the PD-L1 on 1% or more of tumor cells, median overall survival after a median follow-up of 12.8 months was 16.7 months for patients treated with pembrolizumab monotherapy, compared with 12.1 months for patients treated with either paclitaxel or pemetrexed plus carboplatin, reported lead author Gilberto Lopes, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami.
For all three PD-L1 expression groups, the median duration of response was 20.2 months, compared with 10.8-8.3 months for patients in the chemotherapy arm.
“These are responses that are unlike anything that we have seen with chemotherapy in the past for non–small-cell lung cancer,” Dr. Lopes said at a briefing prior to his presentation of the data in a plenary session.
“In addition to that, and probably more importantly, patients had fewer adverse events [with pembrolizumab]. Overall, about 60% had any treatment-related adverse event with pembrolizumab, vs. 90% with chemotherapy,” he added.
‘A true milestone’
ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, said at the briefing that “this study represents a true milestone for the field, because now, for the first time, we can say that among non–small-cell lung cancer patients receiving first-line therapy, the vast majority can receive immunotherapy with pembrolizumab instead of chemotherapy.”
He noted that an earlier study, Keynote-024, showed that pembrolizumab significantly improved progression-free survival in patients with tumors expressing PD-L1 on at least 50% of cells compared with standard platinum-based chemotherapy (10.3 vs. 6 months).
The Keynote-042 investigators enrolled 1,274 patients with locally advanced or metastatic NSCLC, and randomly assigned them to receive either a maximum of 35 cycles of pembrolizumab 200 mg every 3 weeks, or the investigators’ choice of not more than 6 cycles of either paclitaxel/carboplatin or pemetrexed/carboplatin, with optional pemetrexed maintenance for patients with nonsquamous histologies only.
The randomization was stratified by region (Asia vs. non–East Asia), Eastern Cooperative Oncology Group performance status 0 or 1, squamous vs. nonsquamous histology, and PD-L1 expression, or TPS (tumor proportion score) greater than 50% vs. 1%-49%.
As noted before, the primary endpoint of overall survival among all patients with a TPS of 1% or greater was met, with respective median overall survival in the pembrolizumab vs. chemotherapy groups of 16.7 vs. 12.1 months, translating into a hazard ratio favoring pembrolizumab of 0.81 (P = .0018). Respective hazard ratios for the TPS 20% or greater and TPS 50% or greater groups were 0.77 (P = .0020), and 0.69 (P = .0003).
At 12.8 months of median follow-up, 13% of patients assigned to pembrolizumab were still on the drug, and 4.3% of patients were receiving maintenance pemetrexed.
Treatment-related adverse events of any grade occurred in 399 of 636 patients assigned to pembrolizumab (62.7%), vs. 553 of 615 patients assigned to chemotherapy (89.9%).
Grade 3 or greater events occurred in 17.8% vs. 41% of patients, respectively, There were 13 deaths related to therapy in the pembrolizumab arm (2.0%), and 14 in the chemotherapy arm (2.3%).
Adverse events leading to discontinuation were similar between the groups, at 9% and 9.4%, respectively.
There were more immune-mediated adverse events in the pembrolizumab arm (27.8% vs. 7.2%), and of these, grade 3 or greater events occurred in 8% vs. 1.5% of patients, respectively.
There was one immune-mediated death, from pneumonitis, in the immunotherapy arm; there were no deaths related to immune-mediated side effects in the chemotherapy arm.
“I really view this as a ‘double whammy’ for patients,” Dr. Heymach said at the briefing. “Often advances in survival for our lung cancer patients come at the cost of significant toxicities. Here, by contrast, not only are patients living longer and having a much higher likelihood of prolonged survival in years, often instead of months, but they’re also receiving a treatment that has substantially less toxicity across virtually all measures, and this really impacts the day-to-day life of these patients.”
Leena Gandhi, MD, PhD, of the Perlmutter Cancer Center at New York University, the invited discussant at the plenary, agreed that pembrolizumab improves survival, compared with chemotherapy patients with PD-L1 expression levels greater than 1%, but noted that most of the benefit – as also seen in Keynote-024 – was in those patients whose tumors had high levels of PD-L1 expression.
She emphasized that although PD-L1 is an imperfect biomarker, it should still be used to help select patients for therapy, and may be complementary with tumor mutational burden for more precise treatment selection.
“What we know, and what this study adds to, is that PD-L1 really does define a patient population that could receive benefit from pembrolizumab over chemotherapy. Patients with low or no PD-L1 expression likely should get some type of combination therapy,” she said.
“I do think this study extends what we’ve seen from other recent studies, which is that chemotherapy alone is no longer a first-line standard of care in non–small-cell lung cancer,” she added.
Merck funded the study. Dr. Lopes disclosed institutional research funding from Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Dr. Heymach disclosed stock/ownership in Bio-Tree and Cardinal Spine, a consulting or advisory role for Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, and Synta, and institutional research funding from AstraZeneca. Dr. Gandhi reported having no relevant disclosures.
SOURCE: Lobes G et al. ASCO 2018, abstract LBA4.
CHICAGO – Pembrolizumab (Keytruda) as first-line treatment of advanced non–small-cell lung cancer (NSCLC) offered longer overall survival with better tolerability compared with chemotherapy, results of the Keynote-042 phase 3 randomized trial show.
Among 1,274 patients with advanced, previously untreated NSCLC with expression of the PD-L1 on 1% or more of tumor cells, median overall survival after a median follow-up of 12.8 months was 16.7 months for patients treated with pembrolizumab monotherapy, compared with 12.1 months for patients treated with either paclitaxel or pemetrexed plus carboplatin, reported lead author Gilberto Lopes, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami.
For all three PD-L1 expression groups, the median duration of response was 20.2 months, compared with 10.8-8.3 months for patients in the chemotherapy arm.
“These are responses that are unlike anything that we have seen with chemotherapy in the past for non–small-cell lung cancer,” Dr. Lopes said at a briefing prior to his presentation of the data in a plenary session.
“In addition to that, and probably more importantly, patients had fewer adverse events [with pembrolizumab]. Overall, about 60% had any treatment-related adverse event with pembrolizumab, vs. 90% with chemotherapy,” he added.
‘A true milestone’
ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, said at the briefing that “this study represents a true milestone for the field, because now, for the first time, we can say that among non–small-cell lung cancer patients receiving first-line therapy, the vast majority can receive immunotherapy with pembrolizumab instead of chemotherapy.”
He noted that an earlier study, Keynote-024, showed that pembrolizumab significantly improved progression-free survival in patients with tumors expressing PD-L1 on at least 50% of cells compared with standard platinum-based chemotherapy (10.3 vs. 6 months).
The Keynote-042 investigators enrolled 1,274 patients with locally advanced or metastatic NSCLC, and randomly assigned them to receive either a maximum of 35 cycles of pembrolizumab 200 mg every 3 weeks, or the investigators’ choice of not more than 6 cycles of either paclitaxel/carboplatin or pemetrexed/carboplatin, with optional pemetrexed maintenance for patients with nonsquamous histologies only.
The randomization was stratified by region (Asia vs. non–East Asia), Eastern Cooperative Oncology Group performance status 0 or 1, squamous vs. nonsquamous histology, and PD-L1 expression, or TPS (tumor proportion score) greater than 50% vs. 1%-49%.
As noted before, the primary endpoint of overall survival among all patients with a TPS of 1% or greater was met, with respective median overall survival in the pembrolizumab vs. chemotherapy groups of 16.7 vs. 12.1 months, translating into a hazard ratio favoring pembrolizumab of 0.81 (P = .0018). Respective hazard ratios for the TPS 20% or greater and TPS 50% or greater groups were 0.77 (P = .0020), and 0.69 (P = .0003).
At 12.8 months of median follow-up, 13% of patients assigned to pembrolizumab were still on the drug, and 4.3% of patients were receiving maintenance pemetrexed.
Treatment-related adverse events of any grade occurred in 399 of 636 patients assigned to pembrolizumab (62.7%), vs. 553 of 615 patients assigned to chemotherapy (89.9%).
Grade 3 or greater events occurred in 17.8% vs. 41% of patients, respectively, There were 13 deaths related to therapy in the pembrolizumab arm (2.0%), and 14 in the chemotherapy arm (2.3%).
Adverse events leading to discontinuation were similar between the groups, at 9% and 9.4%, respectively.
There were more immune-mediated adverse events in the pembrolizumab arm (27.8% vs. 7.2%), and of these, grade 3 or greater events occurred in 8% vs. 1.5% of patients, respectively.
There was one immune-mediated death, from pneumonitis, in the immunotherapy arm; there were no deaths related to immune-mediated side effects in the chemotherapy arm.
“I really view this as a ‘double whammy’ for patients,” Dr. Heymach said at the briefing. “Often advances in survival for our lung cancer patients come at the cost of significant toxicities. Here, by contrast, not only are patients living longer and having a much higher likelihood of prolonged survival in years, often instead of months, but they’re also receiving a treatment that has substantially less toxicity across virtually all measures, and this really impacts the day-to-day life of these patients.”
Leena Gandhi, MD, PhD, of the Perlmutter Cancer Center at New York University, the invited discussant at the plenary, agreed that pembrolizumab improves survival, compared with chemotherapy patients with PD-L1 expression levels greater than 1%, but noted that most of the benefit – as also seen in Keynote-024 – was in those patients whose tumors had high levels of PD-L1 expression.
She emphasized that although PD-L1 is an imperfect biomarker, it should still be used to help select patients for therapy, and may be complementary with tumor mutational burden for more precise treatment selection.
“What we know, and what this study adds to, is that PD-L1 really does define a patient population that could receive benefit from pembrolizumab over chemotherapy. Patients with low or no PD-L1 expression likely should get some type of combination therapy,” she said.
“I do think this study extends what we’ve seen from other recent studies, which is that chemotherapy alone is no longer a first-line standard of care in non–small-cell lung cancer,” she added.
Merck funded the study. Dr. Lopes disclosed institutional research funding from Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Dr. Heymach disclosed stock/ownership in Bio-Tree and Cardinal Spine, a consulting or advisory role for Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, and Synta, and institutional research funding from AstraZeneca. Dr. Gandhi reported having no relevant disclosures.
SOURCE: Lobes G et al. ASCO 2018, abstract LBA4.
REPORTING FROM ASCO 2018
Key clinical point: Many patients with previously untreated non–small-cell lung cancer could benefit from first-line therapy with the checkpoint inhibitor pembrolizumab.
Major finding: Among all patients with expression of PD-L1 on 1% or more of tumor, overall survival was 16.7 months with pembrolizumab, vs. 12.1 months for chemotherapy.
Study details: Randomized phase 3 trial of 1,274 patients with advanced or metastatic non–small-cell lung cancer.
Disclosures: Merck funded the study. Dr. Lopes disclosed institutional research funding from Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Dr. Heymach disclosed stock/ownership in Bio-Tree and Cardinal Spine, a consulting or advisory role for Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, and Synta, and institutional research funding from AstraZeneca. Dr. Gandhi reported having no relevant disclosures.
Source: Lobes G et al. ASCO 2018, abstract LBA4.
PI3K inhibitor/fulvestrant has modest benefit, serious toxicity in breast cancer
CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?
For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.
“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.
The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.
ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”
He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.
In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.
Taselisib is the first agent in its class to specifically block the PI3K alpha isoform that is found to be mutated in approximately 40% of advanced ER-positive breast cancer. The agent has been shown to offer clinical benefits in early trials for patients with head and neck and some gynecologic cancers.
In the phase 3 SANDPIPER trial, 516 women with locally advanced or metastatic ER-positive, HER2-negative breast cancer that had progressed or recurred following aromatase inhibitor therapy were enrolled and randomly assigned on a 2:1 basis to receive fulvestrant plus taselisib (340 patients) or fulvestrant plus a placebo (176 patients).
As noted, the median progression-free survival was 7.4 months for women who received the combination, compared with 5.4 months for controls. The stratified hazard ratio was 0.70 favoring taselisib (P = .0037).
But also as noted, the addition of taselisib “clearly led to toxicity,” Dr. Baselga said.
Serious adverse events occurred in 32% of patients in the fulvestrant/taselisib group, compared with 8.9% of controls. Grade 3 or greater side effects occurred in 49.5% vs. 16.4%, respectively, and side effects leading to discontinuation of taselisib occurred in 16.8% of patients, vs. 2.3% of those on placebo.
The primary toxicities were gastrointestinal effects, especially diarrhea, which occurred in 60.1% vs. 19.7% of patients (all grades). Hyperglycemia occurred in 40.4% of patients on taselisib, vs. 9.4% on placebo.
Dr. Baselga noted that the secondary endpoints of overall response rate, clinical benefit rate, and duration of response all favored taselisib.
Asked whether taselisib was the right agent in this setting, given the commercial availability of at least two other PI3K inhibitors – idelalisib (Zydelig) and copanlisib (Aliqopa) – Dr. Baselga agreed that another, more specific agent may offer similar or better efficacy with fewer off-target effects. He noted that taselisib is highly active against the alpha isoforms of PI3K, but also hits the delta and gamma isoforms.
“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.
During the oral abstracts session where Dr. Baselga presented the SANDPIPER results, Cynthia X Ma, MD, PhD, from Washington University School of Medicine in St. Louis, the invited discussant, agreed that the trial provides proof of concept that PI3K inhibition may be an effective therapeutic strategy in breast cancer.
“However, the modest progression-free survival improvement and significant toxicity profile does not support its clinical application,” she said.
SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .
CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?
For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.
“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.
The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.
ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”
He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.
In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.
Taselisib is the first agent in its class to specifically block the PI3K alpha isoform that is found to be mutated in approximately 40% of advanced ER-positive breast cancer. The agent has been shown to offer clinical benefits in early trials for patients with head and neck and some gynecologic cancers.
In the phase 3 SANDPIPER trial, 516 women with locally advanced or metastatic ER-positive, HER2-negative breast cancer that had progressed or recurred following aromatase inhibitor therapy were enrolled and randomly assigned on a 2:1 basis to receive fulvestrant plus taselisib (340 patients) or fulvestrant plus a placebo (176 patients).
As noted, the median progression-free survival was 7.4 months for women who received the combination, compared with 5.4 months for controls. The stratified hazard ratio was 0.70 favoring taselisib (P = .0037).
But also as noted, the addition of taselisib “clearly led to toxicity,” Dr. Baselga said.
Serious adverse events occurred in 32% of patients in the fulvestrant/taselisib group, compared with 8.9% of controls. Grade 3 or greater side effects occurred in 49.5% vs. 16.4%, respectively, and side effects leading to discontinuation of taselisib occurred in 16.8% of patients, vs. 2.3% of those on placebo.
The primary toxicities were gastrointestinal effects, especially diarrhea, which occurred in 60.1% vs. 19.7% of patients (all grades). Hyperglycemia occurred in 40.4% of patients on taselisib, vs. 9.4% on placebo.
Dr. Baselga noted that the secondary endpoints of overall response rate, clinical benefit rate, and duration of response all favored taselisib.
Asked whether taselisib was the right agent in this setting, given the commercial availability of at least two other PI3K inhibitors – idelalisib (Zydelig) and copanlisib (Aliqopa) – Dr. Baselga agreed that another, more specific agent may offer similar or better efficacy with fewer off-target effects. He noted that taselisib is highly active against the alpha isoforms of PI3K, but also hits the delta and gamma isoforms.
“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.
During the oral abstracts session where Dr. Baselga presented the SANDPIPER results, Cynthia X Ma, MD, PhD, from Washington University School of Medicine in St. Louis, the invited discussant, agreed that the trial provides proof of concept that PI3K inhibition may be an effective therapeutic strategy in breast cancer.
“However, the modest progression-free survival improvement and significant toxicity profile does not support its clinical application,” she said.
SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .
CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?
For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.
“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.
The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.
ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”
He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.
In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.
Taselisib is the first agent in its class to specifically block the PI3K alpha isoform that is found to be mutated in approximately 40% of advanced ER-positive breast cancer. The agent has been shown to offer clinical benefits in early trials for patients with head and neck and some gynecologic cancers.
In the phase 3 SANDPIPER trial, 516 women with locally advanced or metastatic ER-positive, HER2-negative breast cancer that had progressed or recurred following aromatase inhibitor therapy were enrolled and randomly assigned on a 2:1 basis to receive fulvestrant plus taselisib (340 patients) or fulvestrant plus a placebo (176 patients).
As noted, the median progression-free survival was 7.4 months for women who received the combination, compared with 5.4 months for controls. The stratified hazard ratio was 0.70 favoring taselisib (P = .0037).
But also as noted, the addition of taselisib “clearly led to toxicity,” Dr. Baselga said.
Serious adverse events occurred in 32% of patients in the fulvestrant/taselisib group, compared with 8.9% of controls. Grade 3 or greater side effects occurred in 49.5% vs. 16.4%, respectively, and side effects leading to discontinuation of taselisib occurred in 16.8% of patients, vs. 2.3% of those on placebo.
The primary toxicities were gastrointestinal effects, especially diarrhea, which occurred in 60.1% vs. 19.7% of patients (all grades). Hyperglycemia occurred in 40.4% of patients on taselisib, vs. 9.4% on placebo.
Dr. Baselga noted that the secondary endpoints of overall response rate, clinical benefit rate, and duration of response all favored taselisib.
Asked whether taselisib was the right agent in this setting, given the commercial availability of at least two other PI3K inhibitors – idelalisib (Zydelig) and copanlisib (Aliqopa) – Dr. Baselga agreed that another, more specific agent may offer similar or better efficacy with fewer off-target effects. He noted that taselisib is highly active against the alpha isoforms of PI3K, but also hits the delta and gamma isoforms.
“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.
During the oral abstracts session where Dr. Baselga presented the SANDPIPER results, Cynthia X Ma, MD, PhD, from Washington University School of Medicine in St. Louis, the invited discussant, agreed that the trial provides proof of concept that PI3K inhibition may be an effective therapeutic strategy in breast cancer.
“However, the modest progression-free survival improvement and significant toxicity profile does not support its clinical application,” she said.
SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .
REPORTING FROM ASCO 2018
Key clinical point:
Major finding: The combination of taselisib/fulvestrant extend median progression-free survival by two months.
Study details: Phase 3 randomized trial in 516 women with locally advanced or metastatic ER+/HER2- breast cancer.
Disclosures: The study was funded by F. Hoffman La-Roche. Dr. Baselga had disclosures related to GRAIL, Lilly, and Novartis, Infinity Pharmaceuticals, and Varian Medical Systems, PMV Pharma, and Juno Therapeutics. Dr. Burstein disclosed institutional research funding and speaker’s bureau activities for Novartis. Dr. Ma reported no relevant disclosures.
Source: Baselga et al. ASCO Abstract LBA1006.
Equal treatment, equal or better prostate cancer outcomes for black men
CHICAGO – Black men with advanced prostate cancer have survival with chemotherapy that rivals or surpasses that of white men with advanced disease, and black men with castration-resistant prostate cancer have better outcomes with abiraterone than white men.
Those conclusions come from two studies presented here at the annual meeting of the American Society of Clinical Oncology. Taken together, they suggest that although there may be genetic or biologic differences in cancer presentation among different racial groups, receiving the appropriate care can level out those differences.
In the first study, Susan Halabi, PhD, from Duke University in Durham, N.C., and colleagues pooled data from nine randomized phase 3 chemotherapy trials in men with advanced prostate cancer and found that black and white men had the same median survival, 21 months, but black men had an adjusted hazard ratio [HR} for death of 0.81, compared with white men.
For the subpopulation of African Americans who were enrolled in trials funded by the National Cancer Institute (NCI), the HR for death was 0.76 (P less than .0001).
“The bottom line, in a sense, is that African American men with advanced prostate cancer need to get to an oncologist and ideally need to get on a clinical trial, and if they do, their outcomes are every bit as good as Caucasian men, if not even a little bit better,” Richard Schilsky, MD, chief medical officer of ASCO, said at a briefing prior to presentation of the studies.
In the second study, a prospective clinical trial of abiraterone (Zytiga) in 100 men with metastatic castration-resistant prostate cancer (mCRPC), black men were more likely to have a decline in prostate-specific antigen (PSA), and a longer median time to PSA rise than white men (16.6 vs. 11.5 months), reported Daniel George, MD, also from Duke.
“There’s a 1.6 times greater likelihood that African Americans are diagnosed with prostate cancer, but a 2.4 times greater chance they die from that disease, and although there very well may be multi-factorial reasons for that, I think some of this is genetic,” he said.
Pooled analysis
In the United States, black men are more likely to be diagnosed with prostate cancer in their 40s and 50s than white men and are often diagnosed with advanced-stage and higher grade cancers. Black men also have double the rate of prostate cancer-specific deaths as white men.
Black men, however, are underrepresented in clinical trials, making it difficult to draw firm conclusions about racial differences due to small sample sizes.
To overcome this problem, Dr. Halabi and colleagues pooled data on 8,452 patients with mCRPC - including 7,528 white men and 500 African American men – from nine randomized phase 3 trials of docetaxel and prednisone or a regimen containing those agents.
Median overall survival, the primary endpoint, was 21.0 months for black men and 21.2 months for white men.
In multivariate analysis adjusted for age, PSA, performance status, alkaline phosphatase, hemoglobin, and metastatic sites, the pooled hazard ratio (HR) for black vs. white men was 0.81 (P = .001) for all patients in the study, and when the analysis was restricted to those patients who received only docetaxel and prednisone (4,172), the results were similar, Dr. Halabi said.
“I would argue that what this tells us is pretty striking: that African-American men have potentially better survival by getting conventional therapy,” commented ASCO expert Robert Dreicer, MD, MS, from the University of Virginia in Charlottesville.
“The nihilism associated with prostate cancer in African-American men is not supported by this really interesting work,” he continued. “What it says to us is when we treat those with bad prostate cancer, African Americans, they do well.”
Abiraterone Study
In the abiraterone study, 50 men who self-identified as white and 50 as black were enrolled and treated with abiraterone acetate and prednisone until disease progression or intolerable toxicity.
Radiographic progression-free survival, the primary endpoint, was 16.8 months in each group. As previously noted, however, median PFS was 16.6 months for black patients, vs. 11.5 months for white men. Black men also had a longer median PSA PFS, with 82% of black men having a 30% or greater PSA decline, compared with 78% of white patients. Respective proportions of men having higher declines were 74% vs. 66% experiencing a PSA decline of at least 50%, and 48% vs. 38% having a decline of at least 90%.
Rates of tumor flare, however, were higher among African Americans, at 16% vs. 4%.
Adverse event rates were generally similar between the study arms, although more white than black patients experienced fatigue, and more black than white patients had hypokalemia.
Single-nucletoide polymorphism (SNP) profiling showed differences between the two groups in key genes involved in androgen metabolism and transport, which may explain the improved responses to abiraterone among African Americans.
“We talk about access to care; we have now demonstrated that if you treat African Americans with standard-of-care drugs for advanced prostate cancer, there’s compelling evidence that they respond as well or maybe better than white men,” Dr. Dreicer commented.
“[We are] beginning to understand the differences that drive differential responses,” he continued. “When African-American men are under-represented in clinical trials, the trial outcomes might be different, frankly, because people respond differently to drugs. I think those are the take homes.”
SOURCE: Halabi et al, George et al. ASCO 2018 Abstracts LBA5005 and LBA5009
CHICAGO – Black men with advanced prostate cancer have survival with chemotherapy that rivals or surpasses that of white men with advanced disease, and black men with castration-resistant prostate cancer have better outcomes with abiraterone than white men.
Those conclusions come from two studies presented here at the annual meeting of the American Society of Clinical Oncology. Taken together, they suggest that although there may be genetic or biologic differences in cancer presentation among different racial groups, receiving the appropriate care can level out those differences.
In the first study, Susan Halabi, PhD, from Duke University in Durham, N.C., and colleagues pooled data from nine randomized phase 3 chemotherapy trials in men with advanced prostate cancer and found that black and white men had the same median survival, 21 months, but black men had an adjusted hazard ratio [HR} for death of 0.81, compared with white men.
For the subpopulation of African Americans who were enrolled in trials funded by the National Cancer Institute (NCI), the HR for death was 0.76 (P less than .0001).
“The bottom line, in a sense, is that African American men with advanced prostate cancer need to get to an oncologist and ideally need to get on a clinical trial, and if they do, their outcomes are every bit as good as Caucasian men, if not even a little bit better,” Richard Schilsky, MD, chief medical officer of ASCO, said at a briefing prior to presentation of the studies.
In the second study, a prospective clinical trial of abiraterone (Zytiga) in 100 men with metastatic castration-resistant prostate cancer (mCRPC), black men were more likely to have a decline in prostate-specific antigen (PSA), and a longer median time to PSA rise than white men (16.6 vs. 11.5 months), reported Daniel George, MD, also from Duke.
“There’s a 1.6 times greater likelihood that African Americans are diagnosed with prostate cancer, but a 2.4 times greater chance they die from that disease, and although there very well may be multi-factorial reasons for that, I think some of this is genetic,” he said.
Pooled analysis
In the United States, black men are more likely to be diagnosed with prostate cancer in their 40s and 50s than white men and are often diagnosed with advanced-stage and higher grade cancers. Black men also have double the rate of prostate cancer-specific deaths as white men.
Black men, however, are underrepresented in clinical trials, making it difficult to draw firm conclusions about racial differences due to small sample sizes.
To overcome this problem, Dr. Halabi and colleagues pooled data on 8,452 patients with mCRPC - including 7,528 white men and 500 African American men – from nine randomized phase 3 trials of docetaxel and prednisone or a regimen containing those agents.
Median overall survival, the primary endpoint, was 21.0 months for black men and 21.2 months for white men.
In multivariate analysis adjusted for age, PSA, performance status, alkaline phosphatase, hemoglobin, and metastatic sites, the pooled hazard ratio (HR) for black vs. white men was 0.81 (P = .001) for all patients in the study, and when the analysis was restricted to those patients who received only docetaxel and prednisone (4,172), the results were similar, Dr. Halabi said.
“I would argue that what this tells us is pretty striking: that African-American men have potentially better survival by getting conventional therapy,” commented ASCO expert Robert Dreicer, MD, MS, from the University of Virginia in Charlottesville.
“The nihilism associated with prostate cancer in African-American men is not supported by this really interesting work,” he continued. “What it says to us is when we treat those with bad prostate cancer, African Americans, they do well.”
Abiraterone Study
In the abiraterone study, 50 men who self-identified as white and 50 as black were enrolled and treated with abiraterone acetate and prednisone until disease progression or intolerable toxicity.
Radiographic progression-free survival, the primary endpoint, was 16.8 months in each group. As previously noted, however, median PFS was 16.6 months for black patients, vs. 11.5 months for white men. Black men also had a longer median PSA PFS, with 82% of black men having a 30% or greater PSA decline, compared with 78% of white patients. Respective proportions of men having higher declines were 74% vs. 66% experiencing a PSA decline of at least 50%, and 48% vs. 38% having a decline of at least 90%.
Rates of tumor flare, however, were higher among African Americans, at 16% vs. 4%.
Adverse event rates were generally similar between the study arms, although more white than black patients experienced fatigue, and more black than white patients had hypokalemia.
Single-nucletoide polymorphism (SNP) profiling showed differences between the two groups in key genes involved in androgen metabolism and transport, which may explain the improved responses to abiraterone among African Americans.
“We talk about access to care; we have now demonstrated that if you treat African Americans with standard-of-care drugs for advanced prostate cancer, there’s compelling evidence that they respond as well or maybe better than white men,” Dr. Dreicer commented.
“[We are] beginning to understand the differences that drive differential responses,” he continued. “When African-American men are under-represented in clinical trials, the trial outcomes might be different, frankly, because people respond differently to drugs. I think those are the take homes.”
SOURCE: Halabi et al, George et al. ASCO 2018 Abstracts LBA5005 and LBA5009
CHICAGO – Black men with advanced prostate cancer have survival with chemotherapy that rivals or surpasses that of white men with advanced disease, and black men with castration-resistant prostate cancer have better outcomes with abiraterone than white men.
Those conclusions come from two studies presented here at the annual meeting of the American Society of Clinical Oncology. Taken together, they suggest that although there may be genetic or biologic differences in cancer presentation among different racial groups, receiving the appropriate care can level out those differences.
In the first study, Susan Halabi, PhD, from Duke University in Durham, N.C., and colleagues pooled data from nine randomized phase 3 chemotherapy trials in men with advanced prostate cancer and found that black and white men had the same median survival, 21 months, but black men had an adjusted hazard ratio [HR} for death of 0.81, compared with white men.
For the subpopulation of African Americans who were enrolled in trials funded by the National Cancer Institute (NCI), the HR for death was 0.76 (P less than .0001).
“The bottom line, in a sense, is that African American men with advanced prostate cancer need to get to an oncologist and ideally need to get on a clinical trial, and if they do, their outcomes are every bit as good as Caucasian men, if not even a little bit better,” Richard Schilsky, MD, chief medical officer of ASCO, said at a briefing prior to presentation of the studies.
In the second study, a prospective clinical trial of abiraterone (Zytiga) in 100 men with metastatic castration-resistant prostate cancer (mCRPC), black men were more likely to have a decline in prostate-specific antigen (PSA), and a longer median time to PSA rise than white men (16.6 vs. 11.5 months), reported Daniel George, MD, also from Duke.
“There’s a 1.6 times greater likelihood that African Americans are diagnosed with prostate cancer, but a 2.4 times greater chance they die from that disease, and although there very well may be multi-factorial reasons for that, I think some of this is genetic,” he said.
Pooled analysis
In the United States, black men are more likely to be diagnosed with prostate cancer in their 40s and 50s than white men and are often diagnosed with advanced-stage and higher grade cancers. Black men also have double the rate of prostate cancer-specific deaths as white men.
Black men, however, are underrepresented in clinical trials, making it difficult to draw firm conclusions about racial differences due to small sample sizes.
To overcome this problem, Dr. Halabi and colleagues pooled data on 8,452 patients with mCRPC - including 7,528 white men and 500 African American men – from nine randomized phase 3 trials of docetaxel and prednisone or a regimen containing those agents.
Median overall survival, the primary endpoint, was 21.0 months for black men and 21.2 months for white men.
In multivariate analysis adjusted for age, PSA, performance status, alkaline phosphatase, hemoglobin, and metastatic sites, the pooled hazard ratio (HR) for black vs. white men was 0.81 (P = .001) for all patients in the study, and when the analysis was restricted to those patients who received only docetaxel and prednisone (4,172), the results were similar, Dr. Halabi said.
“I would argue that what this tells us is pretty striking: that African-American men have potentially better survival by getting conventional therapy,” commented ASCO expert Robert Dreicer, MD, MS, from the University of Virginia in Charlottesville.
“The nihilism associated with prostate cancer in African-American men is not supported by this really interesting work,” he continued. “What it says to us is when we treat those with bad prostate cancer, African Americans, they do well.”
Abiraterone Study
In the abiraterone study, 50 men who self-identified as white and 50 as black were enrolled and treated with abiraterone acetate and prednisone until disease progression or intolerable toxicity.
Radiographic progression-free survival, the primary endpoint, was 16.8 months in each group. As previously noted, however, median PFS was 16.6 months for black patients, vs. 11.5 months for white men. Black men also had a longer median PSA PFS, with 82% of black men having a 30% or greater PSA decline, compared with 78% of white patients. Respective proportions of men having higher declines were 74% vs. 66% experiencing a PSA decline of at least 50%, and 48% vs. 38% having a decline of at least 90%.
Rates of tumor flare, however, were higher among African Americans, at 16% vs. 4%.
Adverse event rates were generally similar between the study arms, although more white than black patients experienced fatigue, and more black than white patients had hypokalemia.
Single-nucletoide polymorphism (SNP) profiling showed differences between the two groups in key genes involved in androgen metabolism and transport, which may explain the improved responses to abiraterone among African Americans.
“We talk about access to care; we have now demonstrated that if you treat African Americans with standard-of-care drugs for advanced prostate cancer, there’s compelling evidence that they respond as well or maybe better than white men,” Dr. Dreicer commented.
“[We are] beginning to understand the differences that drive differential responses,” he continued. “When African-American men are under-represented in clinical trials, the trial outcomes might be different, frankly, because people respond differently to drugs. I think those are the take homes.”
SOURCE: Halabi et al, George et al. ASCO 2018 Abstracts LBA5005 and LBA5009
REPORTING FROM ASCO 2018
Key clinical point: Apparent racial disparities in prostate cancer care may be reduced or eliminated with proper care and access to clinical trials.
Major finding: In a pooled analysis, black men with advanced prostate cancer treated with docetaxel prednisone had a 19% lower risk for death than white men,
Study details: Pooled analysis of 9 randomized phase III trials with a total of 8,452 men and a prospective trial with 100 men with advanced prostate cancer.
Disclosures: The study by Halabi et al was funded by Congressionally Directed Medical Research Programs. The study by George et al was funded by Janssen. Dr. Halabi disclosed a consulting or advisory role with Tokai Pharmaceuticals, Eisai, and Bayer, and travel expenses from Bayer. Dr. George disclosed consulting/advising with Janssen and several other pharmaceutical companies, in addition to speakers’ bureau, travel expenses, and honoraria from various companies. He has also received institutional research funding from Exelixis, Genentech/Roche, Janssen Oncology, Novartis, Pfizer, Astellas Pharma, Bristol-Myers Squibb, Millennium, Acerta Pharma, Bayer, Dendreon, and Innocrin Pharma.
Source: Halabi et al, George et al. ASCO 2018 Abstracts LBA5005 and LBA5009.
Heading down the wrong pathway in advanced breast cancer?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – In the SANDPIPER trial, the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) was associated with a small but significant progression-free survival (PFS) benefit, compared with fulvestrant alone in women with advanced estrogen-receptor positive, HER2-negative breast cancer.
That 2-month PFS benefit, described as “modest” by investigators, came at the cost of significant toxicities, with nearly 50% of patients treated with the combination having grade 3 or greater toxicities, compared with 16% of patients treated with fulvestrant alone.
In this video interview from the annual meeting of the American Society of Clinical Oncology, ASCO expert Harold Burstein, MD, PhD, from the Dana-Farber Cancer Institute in Boston, questions whether the PI3K pathway, shown to be targetable in hematologic malignancies, is worth continuing to pursue in breast cancer.
Dr. Burstein had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – In the SANDPIPER trial, the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) was associated with a small but significant progression-free survival (PFS) benefit, compared with fulvestrant alone in women with advanced estrogen-receptor positive, HER2-negative breast cancer.
That 2-month PFS benefit, described as “modest” by investigators, came at the cost of significant toxicities, with nearly 50% of patients treated with the combination having grade 3 or greater toxicities, compared with 16% of patients treated with fulvestrant alone.
In this video interview from the annual meeting of the American Society of Clinical Oncology, ASCO expert Harold Burstein, MD, PhD, from the Dana-Farber Cancer Institute in Boston, questions whether the PI3K pathway, shown to be targetable in hematologic malignancies, is worth continuing to pursue in breast cancer.
Dr. Burstein had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – In the SANDPIPER trial, the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) was associated with a small but significant progression-free survival (PFS) benefit, compared with fulvestrant alone in women with advanced estrogen-receptor positive, HER2-negative breast cancer.
That 2-month PFS benefit, described as “modest” by investigators, came at the cost of significant toxicities, with nearly 50% of patients treated with the combination having grade 3 or greater toxicities, compared with 16% of patients treated with fulvestrant alone.
In this video interview from the annual meeting of the American Society of Clinical Oncology, ASCO expert Harold Burstein, MD, PhD, from the Dana-Farber Cancer Institute in Boston, questions whether the PI3K pathway, shown to be targetable in hematologic malignancies, is worth continuing to pursue in breast cancer.
Dr. Burstein had no disclosures.
REPORTING FROM ASCO 2018
Geriatric assessments enhance patient care in advanced cancer
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – and boosted patient satisfaction, results of a randomized trial show.
In this video interview from the annual meeting of the American Society of Clinical Oncology, Supriya Gupta Mohile, MD, MS, from the University of Rochester, New York, discusses how a standardized written questionnaire and objective tests for physical performance and cognition can enhance the doctor-patient relationship and lead to specific recommendations for interventions, compared with usual care.
Dr. Mohile had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – and boosted patient satisfaction, results of a randomized trial show.
In this video interview from the annual meeting of the American Society of Clinical Oncology, Supriya Gupta Mohile, MD, MS, from the University of Rochester, New York, discusses how a standardized written questionnaire and objective tests for physical performance and cognition can enhance the doctor-patient relationship and lead to specific recommendations for interventions, compared with usual care.
Dr. Mohile had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – and boosted patient satisfaction, results of a randomized trial show.
In this video interview from the annual meeting of the American Society of Clinical Oncology, Supriya Gupta Mohile, MD, MS, from the University of Rochester, New York, discusses how a standardized written questionnaire and objective tests for physical performance and cognition can enhance the doctor-patient relationship and lead to specific recommendations for interventions, compared with usual care.
Dr. Mohile had no relevant financial disclosures.
REPORTING FROM ASCO 2018
Stronger abiraterone response in mCRPC seen in black men
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Results of a prospective clinical trial in 100 men with metastatic castration-resistant prostate cancer (mCRPC) showed that black men were more likely to have a decline in prostate-specific antigen (PSA) and a longer median time to PSA rise in response to treatment with abiraterone (Zytiga) than white men receiving the same treatment (16.8 vs. 11.5 months).
The findings support earlier evidence indicating a stronger response to abiraterone among African Americans compared with Caucasians and suggest that at least some of the observed racial disparities in prostate cancer outcomes could be explained by genetic differences, according to lead study author Daniel George, MD, from Duke University in Durham, N.C.
In this video interview from the annual meeting of the American Society of Clinical Oncology, Dr. George discusses the study findings, as well as issues surrounding the problems of recruiting African Americans for clinical trials and ensuring access to the standard of advanced prostate cancer care for all patients.
Dr. George disclosed consulting or advisory roles and research funding from numerous pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Results of a prospective clinical trial in 100 men with metastatic castration-resistant prostate cancer (mCRPC) showed that black men were more likely to have a decline in prostate-specific antigen (PSA) and a longer median time to PSA rise in response to treatment with abiraterone (Zytiga) than white men receiving the same treatment (16.8 vs. 11.5 months).
The findings support earlier evidence indicating a stronger response to abiraterone among African Americans compared with Caucasians and suggest that at least some of the observed racial disparities in prostate cancer outcomes could be explained by genetic differences, according to lead study author Daniel George, MD, from Duke University in Durham, N.C.
In this video interview from the annual meeting of the American Society of Clinical Oncology, Dr. George discusses the study findings, as well as issues surrounding the problems of recruiting African Americans for clinical trials and ensuring access to the standard of advanced prostate cancer care for all patients.
Dr. George disclosed consulting or advisory roles and research funding from numerous pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Results of a prospective clinical trial in 100 men with metastatic castration-resistant prostate cancer (mCRPC) showed that black men were more likely to have a decline in prostate-specific antigen (PSA) and a longer median time to PSA rise in response to treatment with abiraterone (Zytiga) than white men receiving the same treatment (16.8 vs. 11.5 months).
The findings support earlier evidence indicating a stronger response to abiraterone among African Americans compared with Caucasians and suggest that at least some of the observed racial disparities in prostate cancer outcomes could be explained by genetic differences, according to lead study author Daniel George, MD, from Duke University in Durham, N.C.
In this video interview from the annual meeting of the American Society of Clinical Oncology, Dr. George discusses the study findings, as well as issues surrounding the problems of recruiting African Americans for clinical trials and ensuring access to the standard of advanced prostate cancer care for all patients.
Dr. George disclosed consulting or advisory roles and research funding from numerous pharmaceutical companies.
REPORTING FROM ASCO 2018
