Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non–Small-Cell Lung Cancer in CheckMate 227

Author(s): Julie R. Brahmer, MD1; Jong-Seok Lee, MD, PhD2; Tudor-Eliade Ciuleanu, MD, PhD3; Reyes Bernabe Caro, MD, PhD4; Makoto Nishio, MD, PhD5; Laszlo Urban, MD6; Clarisse Audigier-Valette, MD7; Lorena Lupinacci, MD8; Randeep Sangha, MD9; Adam Pluzanski, MD, PhD10; Jacobus Burgers, MD, PhD11; Mauricio Mahave, MD12; Samreen Ahmed, MD13; Adam J. Schoenfeld, MD14; Luis G. Paz-Ares, MD, PhD15; Martin Reck, MD, PhD16; Hossein Borghaei, DO, MS17; Kenneth J. O’Byrne, MD, PhD18; Ravi G. Gupta, MD19; Judith Bushong, BS19; Li Li, MS, DPH19; Steven I. Blum, MBA19; Laura J. Eccles, PhD19; and Suresh S. Ramalingam, MD20
Source: DOI: 10.1200/JCO.22.01503 Journal of Clinical Oncology 41, no. 6 (February 20, 2023) 1200-1212.
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Combination immunotherapy beats chemotherapy, there is no data to compare against a chemo immunotherapy combination, but is an option for patients who may not tolerate chemotherapy.


We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non–small-cell lung cancer, regardless of tumor programmed death ligand 1 (PD-L1) status.


Adults with stage IV/recurrent non–small-cell lung cancer without EGFR mutations or ALK alterations and with tumor PD-L1 ≥ 1% or < 1% (n = 1739) were randomly assigned. Patients with tumor PD-L1 ≥ 1% were randomly assigned to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 < 1% were randomly assigned to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. End points included exploratory 5-year results for efficacy, safety, and quality of life.


At a minimum follow-up of 61.3 months, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥ 1%) and 19% versus 7% (PD-L1 < 1%). The median duration of response was 24.5 versus 6.7 months (PD-L1 ≥ 1%) and 19.4 versus 4.8 months (PD-L1 < 1%). Among patients surviving 5 years, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued after nivolumab plus ipilimumab discontinuation because of treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥ 1% and < 1% populations). Quality of life in 5-year survivors treated with nivolumab plus ipilimumab was similar to that in the general US population through the 5-year follow-up. No new safety signals were observed.


With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non–small-cell lung cancer.

Author Affiliations

1Johns Hopkins Kimmel Cancer Center, Baltimore, MD;2National University Bundang Hospital, Seongnam, Republic of Korea;3Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania;4Hospital Universitario Virgen Del Rocio, Instituto de Biomedicina de Seville, Seville, Spain;5Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan;6Matrai Gyogyintezet, Mátraháza, Hungary;7Orientation Oncologique, Hôpital Sainte Musse, Toulon, France;8Hospital Italiano De Buenos Aires, Buenos Aires, Argentina;9Cross Cancer Institute, Edmonton, AB, Canada;10Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland;11Netherlands Cancer Institute, Amsterdam, the Netherlands;12Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile;13University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, United Kingdom;14Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY;15Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Clinical Research Unit, Universidad Complutense & CiberOnc, Madrid, Spain;16Airway Research Center North, German Center for Lung Research, Lung Clinic, Grosshansdorf, Germany;17Fox Chase Cancer Center, Philadelphia, PA;18Princess Alexandra Hospital, Translational Research Institute and Queensland University of Technology, Brisbane, Queensland, Australia;19Bristol Myers Squibb, Princeton, NJ;20Winship Cancer Institute, Emory University, Atlanta, GA

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