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CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.
Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.
“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.
The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).
Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.
The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.
In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .
Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.
Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.
“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.
Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.
Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.
While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.
For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.
“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.
Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.
SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.
CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.
Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.
“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.
The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).
Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.
The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.
In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .
Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.
Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.
“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.
Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.
Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.
While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.
For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.
“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.
Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.
SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.
CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.
Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.
“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.
The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).
Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.
The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.
In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .
Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.
Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.
“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.
Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.
Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.
While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.
For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.
“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.
Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.
SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.
REPORTING FROM ASCO 2019