Pembrolizumab Plus Chemotherapy in Squamous Non–Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study

Author(s): Silvia Novello, MD, PhD1; Dariusz M. Kowalski, MD, PhD2; Alexander Luft, MD, PhD3; Mahmut Gümüş, MD4; David Vicente, MD5; Julien Mazières, MD, PhD6; Jeronimo Rodríguez-Cid, MD7; Ali Tafreshi, MD8; Ying Cheng, MD9; Ki Hyeong Lee, MD, PhD10; Alexander Golf, MD11; Shunichi Sugawara, MD, PhD12; Andrew G. Robinson, MD13; Balazs Halmos, MD14; Erin Jensen, MS15; Paul Schwarzenberger, MD16; M. Catherine Pietanza, MD16; and Luis Paz-Ares, MD, PhD17
Source: DOI: 10.1200/JCO.22.01990 Journal of Clinical Oncology 41, no. 11 (April 10, 2023) 1999-2006.
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Three trial updates confirm what we already know and practice.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible patients with previously untreated, metastatic squamous non–small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles. Primary end points were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by blinded independent central review (BICR). Five hundred fifty-nine patients were randomly assigned in the intention-to-treat population (pembrolizumab plus chemotherapy, n = 278; placebo plus chemotherapy, n = 281). The median time from random assignment to data cutoff was 56.9 (range, 49.9-66.2) months. OS and PFS were improved with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (hazard ratio [95% CI], 0.71 [0.59 to 0.85] and 0.62 [0.52 to 0.74]), with 5-year OS rates of 18.4% versus 9.7%, respectively. Toxicity was manageable. Among 55 patients who completed 35 cycles of pembrolizumab, the objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%. Pembrolizumab plus chemotherapy maintained an OS and PFS benefit versus placebo plus chemotherapy in previously untreated, metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.

Author Affiliations

1Department of Oncology, University of Turin, Azienda Ospedaliero Universitaria San Luigi, Turin, Italy2Department of Lung Cancer and Thoracic Tumours, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland3Department of Oncology No. 1 (Thoracic Surgery), Leningrad Regional Clinical Hospital, Saint Petersburg, Russia4Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey5Department of Medical Oncology, Hospital Universitario Virgen Macarena, Sevilla, Spain6Thoracic Oncology, Hôpital Larrey, Centre Hospitalier Universitaire Toulouse, Toulouse, France7Oncology Center, Medica Sur Hospital, Mexico City, Mexico8Wollongong Private Hospital and Wollongong Oncology, Wollongong, NSW, Australia9Department of Oncology, Jilin Cancer Hospital, Changchun, China10Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju, South Korea11Medical Oncology, Universitätskinikum Tübingen, Tuebingen, Germany12Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Miyagi, Japan13Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada14Montefiore Medical Center/Albert Einstein College of Medicine, The Bronx, NY15Biostatistics and Research Decision Sciences, Merck & Co, Inc, Rahway, NJ16Global Clinical Development, Merck & Co, Inc, Rahway, NJ17Department of Medical Oncology, Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Unit, Universidad Complutense & Ciberonc, Madrid, Spain

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