Abstract CT082: Impact of tumor mutation burden on the efficacy of first-line nivolumab in stage iv or recurrent non-small cell lung cancer: An exploratory analysis of CheckMate 026

Abstract

Abstract Background: CheckMate 026 is a randomized trial of nivolumab monotherapy versus platinum doublet chemotherapy in patients with untreated stage IV or recurrent non-small cell lung cancer (NSCLC) and ≥1% programmed death-1 ligand 1 (PD-L1) tumor expression. Nivolumab was not associated with improved progression-free survival (PFS) versus chemotherapy in patients with ≥5% PD-L1 expression, however, nivolumab had a favorable safety profile compared with chemotherapy and overall survival (OS) was similar between treatment arms. In an exploratory analysis, we assessed whether patients with high tumor mutation burden (TMB) may derive enhanced benefit from nivolumab compared with platinum doublet chemotherapy. Methods: TMB scores for missense, somatic mutations were determined in patients with sufficient samples for whole exome sequencing of tumor and matched whole blood DNA. For the initial analyses, patients were equally divided into groups based on TMB tertile distribution. Patients in the low, medium, and high TMB tertiles had 0-99, 100-242, and ≥243 mutations, respectively. Results: Of 541 randomized patients, 312 (57.7%) had evaluable data to determine TMB. The percentage of patients with high TMB was lower in the nivolumab arm than in the chemotherapy arm (29.7% vs 39.0%). Baseline characteristics, PFS, and OS in patients evaluable for TMB were similar to all randomized patients. In patients with high TMB, PFS was improved (median PFS of 9.7 vs. 5.8 months; HR, 0.62; 95% CI, 0.38 to 1.00) and objective response rate was higher with nivolumab versus chemotherapy (46.8% vs 28.3%). OS in patients with high TMB was similar between the 2 treatment arms, which may be attributable in part to a 65% crossover rate to nivolumab in the chemotherapy arm for this subgroup. Conclusions: This is the first pivotal randomized phase 3 trial to incorporate an analysis evaluating TMB and clinical benefit with programmed death-1 inhibitor therapy. The findings of this exploratory retrospective analysis suggest that nivolumab improves ORR and PFS compared with platinum doublet chemotherapy in patients with high TMB. Citation Format: Solange Peters, Benjamin Creelan, Matthew D. Hellmann, Mark A. Socinski, Martin Reck, Prabhu Bhagavatheeswaran, Han Chang, William J. Geese, Luis Paz-Ares, David P. Carbone. Impact of tumor mutation burden on the efficacy of first-line nivolumab in stage iv or recurrent non-small cell lung cancer: An exploratory analysis of CheckMate 026 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT082. doi:10.1158/1538-7445.AM2017-CT082