Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non-small-cell lung cancer Journal Article
| Authors: | Rizvi, N. A.; Hellmann, M. D.; Brahmer, J. R.; Juergens, R. A.; Borghaei, H.; Gettinger, S.; Chow, L. Q.; Gerber, D. E.; Laurie, S. A.; Goldman, J. W.; Shepherd, F. A.; Chen, A. C.; Shen, Y.; Nathan, F. E.; Harbison, C. T.; Antonia, S. |
| Article Title: | Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non-small-cell lung cancer |
| Abstract: | Purpose Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC). Patients and Methods Patients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progressionfree survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression. Results No dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression. Conclusion The safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%. © 2016 by American Society of Clinical Oncology. |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 34 |
| Issue: | 25 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2016-09-01 |
| Start Page: | 2969 |
| End Page: | 2979 |
| Language: | English |
| DOI: | 10.1200/jco.2016.66.9861 |
| PROVIDER: | scopus |
| PUBMED: | 27354481 |
| PMCID: | PMC5569693 |
| DOI/URL: | |
| Notes: | Article -- Presented in part at the Chicago Multidisciplinary Symposium in Thoracic Oncology that took place October 30–November 1, 2014 in Chicago, IL; 50th Annual Meeting of the American Society of Clinical Oncology Annual Meeting that took place May 30–June 3, 2014 in Chicago, IL; and at the European Society for Medical Oncology Congress that took place September 26–September 30, 2014 in Madrid, Spain -- Export Date: 3 October 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work