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

Abstract

PURPOSE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Julie R Brahmer, Jong-Seok Lee, Tudor-Eliade Ciuleanu, Reyes Bernabe Caro, Makoto Nishio, Laszlo Urban, Clarisse Audigier-Valette, Lorena Lupinacci, Randeep Sangha, Adam Pluzanski, Jacobus Burgers, Mauricio Mahave, Samreen Ahmed, Adam J Schoenfeld, Luis G Paz-Ares, Martin Reck, Hossein Borghaei, Kenneth J O'Byrne, Ravi G Gupta, Judith Bushong, Li Li, Steven I Blum, Laura J Eccles, Suresh S Ramalingam
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 41 Issue 6 Pg. 1200-1212 (02 20 2023) ISSN: 1527-7755 [Electronic] United States
• PMID: 36223558 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• Ipilimumab
• Nivolumab

Topics

• Adult
• Humans
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• B7-H1 Antigen (metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics)
• Ipilimumab (therapeutic use)
• Lung Neoplasms (genetics)
• Neoplasm Recurrence, Local (drug therapy)
• Nivolumab (therapeutic use)
• Quality of Life