In KEYNOTE-010 (NCT01905657), pembro provided superior OS over doce in patients (pts) with previously treated advanced NSCLC for the co-primary PD-L1 tumor proportion score (TPS) ≥1% and ≥50% populations, with no difference between pembro doses. To better characterize long-term outcomes in KEYNOTE-010, an analysis based on an additional 6 mo of follow-up was performed.
1034 pts with NSCLC of TPS ≥1% that progressed on ≥2 doses of platinum-doublet chemotherapy were randomized to pembro 2 or 10 mg/kg Q3W or doce 75 mg/m2 Q3W. Crossover upon progression was not permitted until Dec 2015. Response was assessed every 9 wk per RECIST v1.1 by central review. Survival was assessed every 2 mo after study treatment discontinuation. Differences in OS were assessed in the ITT population using the stratified log-rank test.
As of Mar 31, 2016, median follow-up was 19.2 mo and median (range) exposure was 106 d (1-773) for pembro 2 mg/kg, 106 d (1-742) for pembro 10 mg/kg, and 62 d (1-462) for doce. Pembro continued to show superior OS with no difference between doses (Table). 18-mo OS rates were 37% with pembro 2 mg/kg, 43% with pembro 10 mg/kg, and 24% with doce for TPS ≥1% and 46%, 52%, and 24% for TPS ≥50%. ORR was higher with pembro for TPS ≥1% (19% vs 20% vs 10%) and ≥50% (29% vs 32% vs 9%). 60% of pembro and 15% of doce responders, including 65% and 15% with TPS ≥50%, were alive, progression free, and without new anticancer therapy. Treatment-related AE rates remained lower with pembro: 64% vs 67% vs 81% any grade, 13% vs 17% vs 36% grade 3-5.
Superior OS for pembro over doce in pts with previously treated, PD-L1–expressing advanced NSCLC was confirmed with longer follow-up, as was the lack of difference between pembro doses, durability of pembro responses, and, despite longer exposure, a lower rate of treatment-related AEs with pembro. These data support pembro as a standard of care for previously treated, PD-L1–expressing NSCLC.
Clinical trial identification
ClinicalTrials.gov number NCT01905657, originally posted July 18, 2013; EudraCT number 2012-004391-19, originally issued 16-Nov-2012
|Pembro 2 mg/kg||Pembro 10 mg/kg||Doce|
|Median (95% CI), mo||10.5 (9.6-12.4)||13.6 (11.4-17.3)||8.6 (7.9-9.8)|
|HR (95% CI)a||0.72 (0.60-0.87)||0.60 (0.50-0.73)||—|
|HR (95% CI)b||1.19 (0.98-1.45)||—||—|
|Median (95% CI), mo||15.8 (11.0-26.0)||18.8 (12.3-NR)||8.2 (6.6-10.4)|
|HR (95% CI)a||0.54 (0.39-0.73)||0.48 (0.35-0.66)||—|
|HR (95% CI)b||1.18 (0.84-1.64)||—||—|
aPembro vs doce. bPembro 2 mg/kg vs 10 mg/kg.
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
R.S. Herbst: Served as advisory board member for Merck and has received travel expenses, including accommodations, from Merck. P. Baas: Advisory board member: Merck, BMS, Verastem, Celgene; Research funding and travel expenses: Merck, BMS. E. Felip: Consultant/advisor with honoraria: Boehringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene; Speakers' bureau: BMS, Novartis, Roche. J.L. Pérez-Gracia: Speakers' bureau and research funding: Merck. J-H. Kim: Reasearch funding: Roche, Lilly, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck. C. Dubos Arvis: Travel expenses: Novartis, Boehringer. M-J.A. Ahn: Advisory board member: BMS, Ono, MSD, Boehringer Ingelheim, AstraZeneca, Roche G. De Castro Jr.: Advisory board member: MSD, Roche, AstraZeneca; Speakers' bureau: MSD, Roche, AstraZeneca, BMS; Travel expenses: MSD. Y. Shentu, G.M. Lubiniecki: Employment and stock options: Merck & Co., Inc. E.B. Garon: Research funding: AstraZeneca, Boehringer-Ingelheim, BMS, Eli Lilly, Genentech, Merck, Novartis, Pfizer. All other authors have declared no conflicts of interest.