MET amplification and efficacy of nivolumab in patients with non-small cell lung cancer

Abstract Introduction MET amplification is an important genetic alteration in non-small cell lung cancer (NSCLC). Unlike in patients with EGFR and ALK alterations, efficacy of immune checkpoint inhibitors in MET-amplified NSCLC patients remains unknown. Methods An exploratory analysis of a prospective, multi-institutional cohort comprising 200 advanced or recurrent NSCLC patients treated with nivolumab monotherapy was performed, and MET amplification was defined as a MET/CEP7 ratio of ≥2 using fluorescent in situ hybridization. High-level and low-level MET gains were also defined as MET signals ≥10/nuclei and 10> MET signals ≥5/nuclei, respectively. Overall response rates (ORRs) and survival outcomes were evaluated based on the MET gene copy number status. Results Among 175 patients eligible for analysis, MET amplification was detected in 13 (7.4%) tumors. Four (2.3%) high-level and 14 (8.0%) low-level MET gains were also detected. There were no significant differences in ORRs in accordance with the MET gene copy number status. Similarly, no significant differences in both progression-free survival (PFS) and overall survival (OS) were observed between MET-amplified and non-MET-amplified patients (log-rank, P = 0.813 for PFS, and P = 0.855 for OS). Among 101 adenocarcinomas, ORRs in high-level and low-level MET gain patients (50.0% for both) were significantly higher than those of non-MET-gain patients (17.6%), yet survival outcomes for both PFS and OS did not improve. Conclusion MET amplification was not associated with greater benefit of nivolumab treatment in NSCLC patients. Further studies are warranted to prioritize immune checkpoint inhibitors in the treatment regimen for MET-amplified patients.