News Release

First-line pembrolizumab or placebo combined with etoposide and platinum for ES-SCLC: KEYNOTE-604 Long-Term

Reports and Proceedings

International Association for the Study of Lung Cancer

First-Line Pembrolizumab or Placebo Combined With Etoposide and Platinum for ES-SCLC: KEYNOTE-604 Long-Term 

(Vienna—August 9, 2022, 10:10 a.m. CEST)—Long -term follow up of patients with extensive stage small cell lung cancer who were given pembrolizumab and etoposide/platinum (EP) versus placebo + etoposide/platinum as first-line therapy support the continued exploration of pembrolizumab-based combinations for patients with small cell lung cancer. 

In the phase 3 KEYNOTE-604 study of pembrolizumab and etoposide/platinum (EP) versus placebo and etoposide/platinum as first-line therapy for ES-SCLC (NCT03066778), progression-free survival was significantly improved with pembrolizumab + EP versus placebo + EP (HR, 0.75 [95% CI, 0.61-0.91]; P=0.0023) and although the hazard ratio for overall survival favored pembrolizumab + EP, the significance threshold was not met (HR, 0.80 [95% CI, 0.64-0.98]; P=0.0164).  

To build on this earlier study, Dr. Charles Rudin from Memorial Sloan Kettering Cancer Center in New York City presented updated results with a median of 3.5 years of follow-up and outcomes in patients who completed the maximum of 35 cycles of pembrolizumab on study. 

In KEYNOTE-604, eligible patients with previously untreated ES-SCLC were randomized 1:1 to pembrolizumab 200 mg or placebo for up to 35 cycles plus four cycles of standard-dose EP. Dual primary endpoints were overall survival and progression-free survival  (RECISTv1.1, blinded central review) in the intent-to-treat (ITT) population.  

Of the 453 randomized patients in the ITT population (pembrolizumab + EP, n=228; placebo + EP, n=225), median (range) time from randomization to data cutoff (September 21, 2021) was 43.3 (37.8-52.3) months. 54.8% of patients in the pembrolizumab + EP group and 66.2% in the placebo + EP group received subsequent therapy (11.2% vs 22.1% received subsequent immune checkpoint inhibitor). Efficacy outcomes, including overall survival and progression-free survival, were improved with pembrolizumab + EP. 3-year overall survival was 15.5% among patients treated with pembrolizumab + EP vs. 5.9% in those treated with placebo + EP. Grade 3-5 adverse events occurred in 78.9% of patients in the pembrolizumab + EP group and 77.1% of patients in the placebo + EP group. Eighteen patients completed 35 cycles of pembrolizumab (median [range] time from randomization to database cutoff, 42.5 [38.2-49.5] months); of these patients, 14 were alive as of the last assessment before data cutoff. ORR among these patients was 100% (95% CI, 81.5%-100%; 2 CR, 16 PR), and median (range) DOR was not reached (14.1 to 46.8+ months). From the time of completing 35 cycles (~2 years), median OS was not reached (95% CI, 16.6 months to not reached). Two-year OS rate (95% CI) from the time of completing 35 cycles of pembrolizumab was 72.2% (39.5%-89.2%). 

“Pembrolizumab and EP continued to show clinically meaningful improvement in survival and manageable safety versus placebo + EP in patients with previously untreated ES-SCLC; 3-year overall survival rate was over two and a half times higher among patients who received pembrolizumab and EP,” Dr. Rudin reported. “Patients who completed 35 cycles of pembrolizumab had durable responses. Data support the continued exploration of pembrolizumab-based combinations for patients with small cell lung cancer.” 


About the WCLC: 

The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting more than 7,000 researchers, physicians and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit 


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