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

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Perioperative Nivolumab in Resectable Lung Cancer

Perioperative nivolumab (Nivo) showed a 20% 18-month EFPS improvement. This is another option to consider for your patients with stage IIA-IIIB NSCLC. Of note, the study arm received chemo + Nivo x 4 cycles preoperatively, then 12 months of Nivo therapy, and toxicities were as expected.

Read More »

Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer

FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.

Read More »

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.

Read More »

Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor–Mutated Metastatic Non–Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722

This is the same issue as the Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04) article, this one was negative though. A question for the previous trial would be: do we need PDL-1 inhibitor, or just VEGF inhibitor, recall the pts with tumors with high PDL-1 expression did better though, so most likely we need both with chemotherapy.

Read More »