Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non–Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study

Author(s): Gilberto de Castro Jr, MD, PhD1; Iveta Kudaba, MD2; Yi-Long Wu, MD3; Gilberto Lopes, MD4; Dariusz M. Kowalski, MD, PhD5; Hande Z. Turna, MD6; Christian Caglevic, MD7; Li Zhang, MD8; Boguslawa Karaszewska, MD9; Konstantin K. Laktionov, MD10; Vichien Srimuninnimit, MD11; Igor Bondarenko, MD12; Kaoru Kubota, MD, PhD13; Rinee Mukherjee, PhD14; Jianxin Lin, MS14; Fabricio Souza, MD14; Tony S.K. Mok, MD15; and Byoung Chul Cho, MD, PhD16
Source: DOI: 10.1200/JCO.21.02885 Journal of Clinical Oncology 41, no. 11 (April 10, 2023) 1986-1991.
Original Article
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Confirms what we already know. No real surprises.
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 results from the phase III KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894). Eligible patients with locally advanced/metastatic non–small-cell lung cancer (NSCLC) without EGFR/ALK alterations and with programmed death ligand-1 (PD-L1) tumor proportion score (TPS) ≥ 1% received pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) for 4-6 cycles with optional maintenance pemetrexed. Primary end points were overall survival (OS) in PD-L1 TPS ≥ 50%, ≥ 20%, and ≥ 1% groups. Patients who completed 35 cycles of pembrolizumab with ≥ stable disease could begin second-course pembrolizumab upon progression. One thousand two hundred seventy‐four patients were randomly assigned (pembrolizumab, n = 637; chemotherapy, n = 637). Median follow-up time was 61.1 (range, 50.0-76.3) months. OS outcomes favored pembrolizumab (v chemotherapy) regardless of PD-L1 TPS (hazard ratio [95% CI] for TPS ≥ 50%, 0.68 [0.57 to 0.81]; TPS ≥ 20%, 0.75 [0.64 to 0.87]; TPS ≥ 1%, 0.79 [0.70 to 0.89]), with estimated 5-year OS rates with pembrolizumab of 21.9%, 19.4%, and 16.6%, respectively. No new toxicities were identified. Objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course pembrolizumab. First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1–positive, locally advanced/metastatic NSCLC without EGFR/ALK alterations and remains a standard of care.

Author Affiliations

1Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil2Latvian Oncology Center, Riga East Clinical University, Riga, Latvia3Guangdong Lung Cancer Institute, Guangdong Provinicial People’s Hospital and Guangdong Academy of Medical Sciences, Guandong, China4Department of Medical Oncology, Sylvester Comprehensive Cancer Center at the University of Miami, FL5Department of Lung Cancer and Chest Tumours, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland6Department of Internal Medicine, Istanbul University‐Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey7Cancer Research Department, Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile8Peking Union Medical College Hospital, Beijing, China9Przychodnia Lekarska KOMED, Konin, Poland10Federal State Budgetary Institution, “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russia11Department of Medicine, Siriraj Hospital, Bangkok, Thailand12Oncology and Medical Radiology Department, Dnipro State Medical Academy, Dnipro, Ukraine13Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital, Tokyo, Japan14Merck & Co, Inc, Rahway, NJ15Clinical Oncology, State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Shatin, Hong Kong, China16Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea

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