Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: Randomized, double-blind, phase III KEYNOTE-604 study Journal Article


Authors: Rudin, C. M.; Awad, M. M.; Navarro, A.; Gottfried, M.; Peters, S.; Csőszi, T.; Cheema, P. K.; Rodriguez-Abreu, D.; Wollner, M.; Yang, J. C. H.; Mazieres, J.; Orlandi, F. J.; Luft, A.; Gümüş, M.; Kato, T.; Kalemkerian, G. P.; Luo, Y.; Ebiana, V.; Pietanza, M. C.; Kim, H. R.; on behalf of the KEYNOTE-604 Investigators
Article Title: Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: Randomized, double-blind, phase III KEYNOTE-604 study
Abstract: PURPOSE: Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus etoposide and platinum (EP) with placebo plus EP for patients with previously untreated extensive-stage (ES) SCLC. METHODS: Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks or saline placebo for up to 35 cycles plus 4 cycles of EP. Primary end points were progression-free survival (PFS; RECIST version 1.1, blinded central review) and overall survival (OS) in the intention-to-treat population. Objective response rate (ORR) and duration of response were secondary end points. Prespecified efficacy boundaries were one-sided P = .0048 for PFS and .0128 for OS. RESULTS: Of the 453 participants, 228 were randomly assigned to pembrolizumab plus EP and 225 to placebo plus EP. Pembrolizumab plus EP significantly improved PFS (hazard ratio [HR], 0.75; 95% CI, 0.61 to 0.91; P = .0023). Twelve-month PFS estimates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP. Although pembrolizumab plus EP prolonged OS, the significance threshold was not met (HR, 0.80; 95% CI, 0.64 to 0.98; P = .0164). Twenty-four-month OS estimates were 22.5% and 11.2%, respectively. ORR was 70.6% in the pembrolizumab plus EP group and 61.8% in the placebo plus EP group; the estimated proportion of responders remaining in response at 12 months was 19.3% and 3.3%, respectively. In the pembrolizumab plus EP and placebo plus EP groups, respectively, any-cause adverse events were grade 3-4 in 76.7% and 74.9%, grade 5 in 6.3% and 5.4%, and led to discontinuation of any drug in 14.8% and 6.3%. CONCLUSION: Pembrolizumab plus EP significantly improved PFS compared with placebo plus EP as first-line therapy for patients with ES-SCLC. No unexpected toxicities were seen with pembrolizumab plus EP. These data support the benefit of pembrolizumab in ES-SCLC.
Journal Title: Journal of Clinical Oncology
Volume: 38
Issue: 21
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2020-07-20
Start Page: 2369
End Page: 2379
Language: English
DOI: 10.1200/jco.20.00793
PUBMED: 32468956
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 August 2020 -- Source: Scopus
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  1. Charles Rudin
    249 Rudin