TY - JOUR
T1 - 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
AU - Gettinger, Scott N.
AU - Horn, Leora
AU - Gandhi, Leena
AU - Spigel, David R.
AU - Antonia, Scott J.
AU - Rizvi, Naiyer A.
AU - Powderly, John D.
AU - Heist, Rebecca S.
AU - Carvajal, Richard D.
AU - Jackman, David M.
AU - Sequist, Lecia V.
AU - Smith, David C.
AU - Leming, Philip
AU - Carbone, David P.
AU - Pinder-Schenck, Mary C.
AU - Topalian, Suzanne L.
AU - Hodi, F. Stephen
AU - Sosman, Jeffrey A.
AU - Sznol, Mario
AU - McDermott, David F.
AU - Pardoll, Drew M.
AU - Sankar, Vindira
AU - Ahlers, Christoph M.
AU - Salvati, Mark
AU - Wigginton, Jon M.
AU - Hellmann, Matthew D.
AU - Kollia, Georgia D.
AU - Gupta, Ashok K.
AU - Brahmer, Julie R.
N1 - Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
PY - 2015/6/20
Y1 - 2015/6/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2014.58.3708
DO - 10.1200/JCO.2014.58.3708
M3 - Article
C2 - 25897158
AN - SCOPUS:84936749833
SN - 0732-183X
VL - 33
SP - 2004
EP - 2012
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 18
ER -