Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451

• Type of Material: Article
• Authors: Taofeek Owonikoko, Emory University; Keunchil Park, Sungkyunkwan University; Ramaswamy Govindan, Washington University; Neal Ready, Duke University; Martin Reck, LungClinic; Solange Peters, Lausanne University Hospital; Shaker R Dakhil, Canc Ctr Kansas; Alejandro Navarro, Vall d'Hebron University Hospital; Jerónimo Rodriguez-Cid, Med Sur Inst Nacl Enfermedades Resp; Michael Schenker, Centrul de Oncologie Sf Nectarie; Jong-Seok Lee, Seoul National University; Vanesa Gutierrez, Hospital Regional Universitario de Málaga; Ivor Percent, Florida Cancer Specialists; Daniel Morgensztern, Washington University; Carlos H Barrios, Pontificia Univ Catolica Rio Grande Sul PUCRS; Laurent Greillier, Aix Marseille University; Sofia Baka, Interbalkan European Medical Center; Miten Patel, Cancer Specialists of North Florida; Wen Hong Lin, Bristol Myers Squibb; Giovanni Selvaggi, Bristol Myers Squibb; Christine Baudelet, Bristol Myers Squibb; Jonathan Baden, Bristol Myers Squibb; Dimple Pandya, Bristol Myers Squibb; Parul Doshi, Bristol Myers Squibb; Hye R Kim, Yonsei University
• Language: English
• Date: 2021-04-20
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by American Society of Clinical Oncology
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.20.02212
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 39
• Issue: 12
• Start Page: 1349
• End Page: +
• Grant/Funding Information: See publication for list of funding groups
• Keywords: PLUS IPILIMUMAB; Oncology; EXPRESSION; Science & Technology; CHEMOTHERAPY; OPEN-LABEL; PEMBROLIZUMAB; Life Sciences & Biomedicine; MULTICENTER; PD-L1
• Research Categories: Health Sciences, Oncology

Abstract

PURPOSE In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC. METHODS Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after # 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for # 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested. RESULTS Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; P 5 .37; median, 9.2 v 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden $ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%). CONCLUSION Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.