Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non–Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study

Author(s): Marina C. Garassino, MD1,2; Shirish Gadgeel, MD3; Giovanna Speranza, MD, MSc4; Enriqueta Felip, MD, PhD5; Emilio Esteban, MD6; Manuel Dómine, MD7; Maximilian J. Hochmair, MD8; Steven F. Powell, MD9; Helge G. Bischoff, MD10; Nir Peled, MD11; Francesco Grossi, MD12; Ross R. Jennens, MBBS13; Martin Reck, MD, PhD14; Rina Hui, MBBS, PhD15; Edward B. Garon, MD16; Takayasu Kurata, MD17; Jhanelle E. Gray, MD18; Paul Schwarzenberger, MD19; Erin Jensen, MS19; M. Catherine Pietanza, MD19; and Delvys Rodríguez-Abreu, MD, PhD20
Source: DOI: 10.1200/JCO.22.01989 Journal of Clinical Oncology 41, no. 11 (April 10, 2023) 1992-1998.
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 on the 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 present 5-year outcomes from the phase 3 KEYNOTE-189 study (ClinicalTrials.gov identifier: NCT02578680). Eligible patients with previously untreated metastatic nonsquamous non–small-cell lung cancer without EGFR/ALK alterations were randomly assigned 2:1 to pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles with pemetrexed and investigator’s choice of carboplatin/cisplatin for four cycles, followed by maintenance pemetrexed until disease progression or unacceptable toxicity. Primary end points were overall survival (OS) and progression-free survival (PFS). Among 616 randomly assigned patients (n = 410, pembrolizumab plus pemetrexed-platinum; n = 206, placebo plus pemetrexed-platinum), median time from random assignment to data cutoff (March 8, 2022) was 64.6 (range, 60.1-72.4) months. Hazard ratio (95% CI) for OS was 0.60 (0.50 to 0.72) and PFS was 0.50 (0.42 to 0.60) for pembrolizumab plus platinum-pemetrexed versus placebo plus platinum-pemetrexed. 5-year OS rates were 19.4% versus 11.3%. Toxicity was manageable. Among 57 patients who completed 35 cycles of pembrolizumab, objective response rate was 86.0% and 3-year OS rate after completing 35 cycles (approximately 5 years after random assignment) was 71.9%. Pembrolizumab plus pemetrexed-platinum maintained OS and PFS benefits versus placebo plus pemetrexed-platinum, regardless of programmed cell death ligand-1 expression. These data continue to support pembrolizumab plus pemetrexed-platinum as a standard of care in previously untreated metastatic non–small-cell lung cancer without EGFR/ALK alterations.

Author Affiliations

1Knapp Center for Biomedical Discovery, University of Chicago Medicine & Biological Sciences, Chicago, IL2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy3Henry Ford Cancer Institute/Henry Ford Health, Detroit, MI4Centre Integré de Cancérologie de la Montérégie, Hôpital Charles-Le Moyne, Greenfield Park, QC, Canada5Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain6Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain7Department of Oncology, Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain8Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria9Hematology and Oncology, Sanford Cancer Center, Sioux Falls, SD10Thoraxklinik, Heidelberg, Germany11Department of Oncology, Shaare Zedek Medical Center, Jerusalem, Israel12Medical Oncology Division, University of Insubria, Varese, Italy13Department of Medical Oncology, Epworth Healthcare, Richmond, VIC, Australia14LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany15Department of Medical Oncology, Westmead Hospital and University of Sydney, Sydney, NSW, Australia16Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA17Department of Thoracic Oncology, Kansai Medical University Hospital, Osaka, Japan18Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL19Merck & Co, Inc, Rahway, NJ20Complejo 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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