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.

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.

• Authors: 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 McDermott, Drew M Pardoll, Vindira Sankar, Christoph M Ahlers, Mark Salvati, Jon M Wigginton, Matthew D Hellmann, Georgia D Kollia, Ashok K Gupta, Julie R Brahmer
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 18 Pg. 2004-12 (Jun 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25897158 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Nivolumab

Topics

• 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
• Programmed Cell Death 1 Receptor (metabolism)
• Treatment Outcome