Platinum-based doublet chemo is the standard first-line therapy for advanced NSCLC without a treatable oncogenic aberration. Pembro (anti–PD-1) is approved in the US and EU for previously treated, PD-L1–expressing advanced NSCLC. KEYNOTE-024 (NCT02142738) is an open-label, phase 3 study of pembro vs platinum-doublet chemo as first-line therapy for advanced NSCLC of PD-L1 TPS ≥50% without treatable EGFR mutations or ALK translocations.
Patients (pts) were randomized to 35 cycles of pembro 200 mg Q3W or 4-6 cycles of investigator's choice of carboplatin or cisplatin + pemetrexed, carboplatin or cisplatin + gemcitabine, or carboplatin + paclitaxel, with optional pemetrexed maintenance for nonsquamous NSCLC. Pts in the chemo arm could crossover to pembro upon PD. Response was assessed every 9 wk (RECIST v1.1, central imaging vendor). Primary end point was PFS. Secondary end points were OS, ORR, and safety. Differences in PFS and OS were assessed in the ITT population using the stratified log-rank test. At the prespecified second interim analysis (data cutoff, May 9, 2016), the study had 97% power to detect a HR of 0.55 for PFS at a 1-sided α = 2.0%.
From Sep 19, 2014, to Oct 29, 2015, 305 pts from 16 countries were randomized: 154 to pembro, 151 to chemo. After a median follow-up of 11.2 mo, 48% of pts remained on pembro, 10% remained on chemo, and 44% crossed over from chemo to pembro upon PD. With 189 events, pembro significantly prolonged PFS over chemo (HR 0.50, 95% CI 0.37-0.68, P < 0.001; median 10.3 mo vs 6.0 mo). With 108 deaths, pembro also significantly prolonged OS (HR 0.60, 95% CI 0.41-0.89, P = 0.005; 6-mo OS 80% vs 72%). Pembro was also associated with higher ORR (45% vs 28%), longer response duration (median NR vs 6.3 mo), and lower incidence of any-grade (73% vs 90%) and grade 3-5 (27% vs 53%) treatment-related AEs.
Pembro demonstrated superior PFS and OS over platinum-based chemo in pts with advanced NSCLC of PD-L1 TPS ≥50%. Along with the lower rate of treatment-related AEs, these data suggest pembro may be the new standard of care for first-line therapy of PD-L1–expressing advanced NSCLC without treatable oncogenic aberrations.
Clinical trial identification
ClinicalTrials.gov number NCT02142738, originally posted May 16, 2014; EudraCT number 2014-000323-25, originally issued 27-Mar-2014
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
M. Reck: Served as Advisory board member for Roche, Lilly, BMS, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. Also, served on Speakers' bureau for Roche, Lilly, BMS, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. D. Rodríguez-Abreu: Advisory board member, speakers' bureau, and travel expenses: BMS, MSD, Boehringer, Roche. A.G. Robinson: Speakers' bureau: Merck, Pfizer, Roche, Novartis. R. Hui: Advisory board member: MSD, AstraZeneca, Pfizer, Novartis. N. Peled: Speakers' bureau and travel expenses: MSD. A. Tafreshi: Advisory board member: Merck, Ipsen. M. O'Brien: Advisory board member: MSD, Bristol-Myers Squibb, Abbive, Boehringer Ingelheim, Pierre Fabre; Travel expenses: Bristol-Myers Squibb. K. Hotta: Speakers' bureau: Chugai, Lilly, AstraZeneca, Daiichi-Sankyo Pharmaceutical, Boehringer-Ingelheim, Nihon Kayaku, Taiho Pharmaceutical, and Sanofi-Aventis; Research funding: Merck, Chgai, Lilly. M. Leiby, G.M. Lubiniecki, Y. Shentu, R. Rangwala: Employment and stock options: Merck & Co., Inc. J.R. Brahmer: Advisory board: Bristol-Myers Squibb, MedImmune/AstraZeneca, Merck; Advisory board: Bristol-Myers Squibb (uncompensated), Celgene, Lilly, MedImmume/AstraZeneca. All other authors have declared no conflicts of interest.