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

Scott N. Gettinger, Leora Horn, Leena Gandhi, David R. Spigel, Scott J. Antonia, Naiyer A. Rizvi, John D. Powderly, Rebecca S. Heist, Richard D. Carvajal, David M. Jackman, Lecia V. Sequist, David C. Smith, Philip Leming, David P. Carbone, Mary C. Pinder-Schenck, Suzanne L. Topalian, F. Stephen Hodi, Jeffrey A. Sosman, Mario Sznol, David F. McDermottDrew M. Pardoll, Vindira Sankar, Christoph M. Ahlers, Mark Salvati, Jon M. Wigginton, Matthew D. Hellmann, Georgia D. Kollia, Ashok K. Gupta, Julie R. Brahmer

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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 and Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2004-2012
Number of pages9
JournalJournal of Clinical Oncology
Volume33
Issue number18
DOIs
StatePublished - Jun 20 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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