Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 33; no. 18; pp. 2004 - 2012
• Main Authors: Gettinger, Scott N, Horn, Leora, Gandhi, Leena, Spigel, David R, Antonia, Scott J, Rizvi, Naiyer A, Powderly, John D, Heist, Rebecca S, Carvajal, Richard D, Jackman, David M, Sequist, Lecia V, Smith, David C, Leming, Philip, Carbone, David P, Pinder-Schenck, Mary C, Topalian, Suzanne L, Hodi, F Stephen, Sosman, Jeffrey A, Sznol, Mario, McDermott, David F, Pardoll, Drew M, Sankar, Vindira, Ahlers, Christoph M, Salvati, Mark, Wigginton, Jon M, Hellmann, Matthew D, Kollia, Georgia D, Gupta, Ashok K, Brahmer, Julie R
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.06.2015
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Cohort Studies; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Male; Middle Aged; Neoplasm Metastasis; Nivolumab; ORIGINAL REPORTS; Programmed Cell Death 1 Receptor - metabolism; Treatment Outcome
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2014.58.3708

Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial. Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.