Pembrolizumab (pembro) has shown efficacy in NSCLC, with improved outcomes in pts with greater tumor PD-L1 expression. KEYNOTE-010 (NCT01905657) compared the efficacy and safety of 2 pembro doses with those of docetaxel for PD-L1+ advanced NSCLC that progressed after ≥2 platinum-doublet chemotherapy cycles, with an appropriate tyrosine kinase inhibitor also required for pts with EGFR sensitizing mutations or ALK translocations.
Pts were stratified by ECOG PS (0 vs 1), region (East Asia vs non–East Asia), and PD-L1 expression level (tumor proportion score [TPS] ≥50% vs 1%-49%) and randomized 1:1:1 to pembro 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W. Treatment was continued up to 24 mo or until progression or intolerable toxicity. Response was assessed every 9 wk. Primary end points were OS and PFS (RECIST v1.1, central review) in the TPS ≥50% stratum and total population (ie, TPS ≥1%). ORR was a secondary end point. At final analysis, the study had ≥80% power to detect a 0.70 HR for OS in the total population (1-sided α = 0.825%).
From Aug 2013 to Apr 2015, 1034 pts from 24 countries were randomized: 345 to pembro 2 mg/kg, 346 to pembro 10 mg/kg, and 343 to docetaxel. Pembro significantly improved OS over docetaxel for TPS ≥50% and ≥1% (Table). Pembro significantly improved PFS for TPS ≥50% and numerically improved PFS for TPS ≥1% (Table). ORR was significantly higher with pembro for TPS ≥50% (30.2% at 2 mg/kg vs 29.1% at 10 mg/kg vs 7.9% with docetaxel, P < 0.0001 for both doses) and ≥1% (18.0% vs 18.5% vs 9.3%, P < 0.0005 for both doses). Pembro was associated with fewer grade 3-5 drug-related AEs (12.7% at 2 mg/kg vs 16.0% at 10 mg/kg vs 35.3% with docetaxel). Drug-related deaths occurred in 0.9%, 0.9%, and 1.6% of patients.
|Pembro 2 mg/kg||Pembro 10 mg/kg||Docetaxel|
|OS, TPS ≥50%|
|Median (95% CI), mo||14.9 (10.4-NR)||17.3 (11.8-NR)||8.2 (6.4-10.7)|
|HR (95% CI)||0.54 (0.38-0.77)||0.50 (0.36-0.70)||â|
|OS, TPS ≥1%|
|Median (95% CI), mo||10.4 (9.4-11.9)||12.7 (10.0-17.3)||8.5 (7.5-9.8)|
|HR (95% CI)||0.71 (0.58-0.88)||0.61 (0.49-0.75)||â|
|PFS, TPS ≥50%|
|Median (95% CI), mo||5.0 (4.0-6.5)||5.2 (4.1-8.1)||4.1 (3.6-4.3)|
|HR (95% CI)||0.59 (0.44-0.78)||0.59 (0.45-0.78)||â|
|PFS, TPS ≥1%|
|Median (95% CI), mo||3.9 (3.1-4.1)||4.0 (2.7-4.3)||4.0 (3.1-4.2)|
|HR (95% CI)||0.88 (0.74-1.05)||0.79 (0.66-0.94)||â|
Pembro 2 and 10 mg/kg Q3W significantly prolonged OS compared with docetaxel and showed a favorable benefit-to-risk profile in PD-L1+ advanced NSCLC after progression on platinum-based therapy.
Clinical trial identification
ClinicalTrials.gov identifier NCT01905657; EudraCT number 2012-004391-19.
R.S. Herbst: Advisory board member for Merck. E. Felip: Advisory board member for Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Roche. J.L. Perez-Gracia: Corporate-sponsored research from Merck. E.B. Garon: Relationships with AstraZeneca, Bristol-Myers Squibb, Genentech, Merck, Pfizer, and Novartis. R. Gervais: Advisory board member for Bristol-Myers Squibb, Clovis, Merck, and Pfizer. M.-J. Ahn: Advisory board member for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, and Eli-Lilly. G. De Castro Jr.: Corporate-sponsored research from AstraZeneca, Bristol-Myers Squibb, Genentech, Merck Sharp & Dohme, Merck Serono, Pfizer, and Roche. G.M. Lubiniecki, Y. Shentu and E. Im: Employee of and holds stock in Merck & Co., Inc. P. Baas: Advisory board member for Adaro, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Pfizer. Corporate-sponsored research from Bristol-Myers Squibb and Merck Sharp & Dohme. All other authors have declared no conflicts of interest.