A Randomized,Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407 |
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| Institution: | 1. Department of Medical Oncology, Hospital Universitario 12 de Octubre, H12o-CNIO Lung Cancer Unit, Universidad Complutense & Ciberonc, Madrid, Spain;2. Department of Clinical Oncology, Hospital Universitario Virgen Macarena, Sevilla, Spain;3. Wollongong Oncology, Wollongong Private Hospital, Wollongong, New South Wales, Australia;4. Cancer Centre of Southeastern Ontario, Kingston General Hospital, Kingston, Ontario, Canada;5. Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele, Catania, Italy;6. Hôpital Larrey, Centre Hospitalier Universitaire Toulouse, Toulouse, France;7. Universitätskinikum Tübingen, Tuebingen, Germany;8. Department of Medical Oncology, Trakya University, Edirne, Turkey;9. Veszprém Megyei Tüd?gyógyintézet Farkasgyep?, Farkasgyep?, Hungary;10. Oncology Center, Medica Sur Hospital, Mexico City, Mexico;11. Department of Medicine and Surgery, Kyushu University Hospital, Fukuoka, Japan;12. Department of Hematology-Oncology, Inje University College of Medicine, Busan, South Korea;13. Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland;14. Pyatigorsk Oncology Dispensary, State Healthcare Institute, Pyatigorsk, Russia;15. Department of Oncology, Cancer Hospital of Jilin Province, Changchun, People’s Republic of China;p. Merck & Co., Inc., Kenilworth, New Jersey;q. HTA Statistics Europe, Merck Sharp & Dohme, Brussels, Belgium;r. Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York |
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| Abstract: | IntroductionIn the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next line of treatment.MethodsEligible patients were randomized to chemotherapy plus either pembrolizumab (n = 278) or placebo (n = 281). After positive results from the second interim analysis, patients still receiving placebo could cross over to pembrolizumab monotherapy at the time of confirmed progressive disease. The primary end points were OS and PFS. PFS-2 (time from randomization to progression on next-line treatment/death, whichever occurred first) was an exploratory end point.ResultsAfter median (range) follow-up of 14.3 (0.1–31.3) months, pembrolizumab plus chemotherapy continued to exhibit a clinically meaningful improvement over placebo plus chemotherapy in OS (median, 17.1 mo 95% confidence interval (CI): 14.4?19.9] versus 11.6 mo 95% CI: 10.1?13.7]; hazard ratio HR], 0.71 95% CI: 0.58?0.88]) and PFS (median, 8.0 mo 95% CI: 6.3?8.4] versus 5.1 mo 95% CI: 4.3?6.0]; HR, 0.57 95% CI: 0.47?0.69]). PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy (HR, 0.59 95% CI: 0.49?0.72]). Grade 3 to 5 adverse events occurred in 74.1% and 69.6% of patients receiving pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively.ConclusionsPembrolizumab plus chemotherapy continued to exhibit substantially improved OS and PFS in patients with metastatic squamous NSCLC. The PFS-2 outcomes support pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC. |
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| Keywords: | PD-L1 Pembrolizumab Chemotherapy Squamous non–small-cell lung cancer |
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