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

• Published in: Journal of clinical oncology Vol. 41; no. 6; pp. 1200 - 1212
• Main Authors: Brahmer, Julie R, Lee, Jong-Seok, Ciuleanu, Tudor-Eliade, Bernabe Caro, Reyes, Nishio, Makoto, Urban, Laszlo, Audigier-Valette, Clarisse, Lupinacci, Lorena, Sangha, Randeep, Pluzanski, Adam, Burgers, Jacobus, Mahave, Mauricio, Ahmed, Samreen, Schoenfeld, Adam J, Paz-Ares, Luis G, Reck, Martin, Borghaei, Hossein, O'Byrne, Kenneth J, Gupta, Ravi G, Bushong, Judith, Li, Li, Blum, Steven I, Eccles, Laura J, Ramalingam, Suresh S
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 20-02-2023
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B7-H1 Antigen - metabolism; Carcinoma, Non-Small-Cell Lung - genetics; Humans; Ipilimumab - therapeutic use; Lung Neoplasms - genetics; Neoplasm Recurrence, Local - drug therapy; Nivolumab - therapeutic use; Quality of Life; RAPID COMMUNICATIONS
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.22.01503

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
mutations or
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.