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
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- Charles M. Rudin
- Memorial Sloan Kettering Cancer Center, New York, NY
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- Mark M. Awad
- Dana-Farber Cancer Institute, Boston, MA
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- Alejandro Navarro
- Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain
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- Maya Gottfried
- Meir Medical Center, Kfar-Saba, Israel
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- Solange Peters
- Lausanne University Hospital, Lausanne, Switzerland
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- Tibor Csőszi
- Hetényi Géza Kórház Onkológiai Központ, Szolnok, Hungary
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- Parneet K. Cheema
- William Osler Health System, University of Toronto, Brampton, Ontario, Canada
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- Delvys Rodriguez-Abreu
- Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
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- Mirjana Wollner
- Rambam Medical Center, Haifa, Israel
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- James Chih-Hsin Yang
- National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan
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- Julien Mazieres
- Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France
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- Francisco J. Orlandi
- Oncología-Health and Care, Santiago, Chile
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- Alexander Luft
- Leningrad Regional Clinical Hospital, St Petersburg, Russia
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- Mahmut Gümüş
- Istanbul Medeniyet University Hospital, Istanbul, Turkey
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- Terufumi Kato
- Kanagawa Cancer Center, Yokohama, Japan
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- Gregory P. Kalemkerian
- University of Michigan, Ann Arbor, MI
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- Yiwen Luo
- Merck & Co, Kenilworth, NJ
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- Victoria Ebiana
- Merck & Co, Kenilworth, NJ
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- M. Catherine Pietanza
- Merck & Co, Kenilworth, NJ
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- Hye Ryun Kim
- Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
説明
<jats:sec><jats:title>PURPOSE</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> 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%. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> 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. </jats:p></jats:sec>
収録刊行物
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- Journal of Clinical Oncology
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Journal of Clinical Oncology 38 (21), 2369-2379, 2020-07-20
American Society of Clinical Oncology (ASCO)