Somatic mutations in non-small cell lung cancer and their correlation with overall survival, tumor mutation burden, and programmed-death cell ligand-1 (PD-L1) status.

Abstract

e14752 Background: In recent years, treatments for non-small cell lung cancer (NSCLC) have expanded to include targeted therapies and immune checkpoint inhibitors in addition to traditional treatments. These newer modalities of treatment require testing with next-generation sequencing (NGS) testing, which offers testing for hundreds of somatic mutations, both with known and unknown significance. Tumor mutation burden (TMB), which is the number of mutations per coding sequence, is also reported on NGS. Patients with targetable mutations or a high TMB have been found to have improved survival and higher responses to immunotherapy, respectively. We wanted to investigate whether the total number of mutations (both with known and unknown significance) had any association with PD-L1 status, TMB and overall survival. Methods: This was a single institution, retrospective study of 51 patients with stage I-IV NSCLC. Results: In our study, we found that there was a significant correlation between the number of mutations and TMB in all patients with NSCLC (p = 0.001), including adenocarcinoma (p = 0.005). We found that the number of known mutations, mutations of unknown significance and total overall mutations did not have a significant correlation with survival (p = 0.708, p = 0.808, and p = 0.639, respectively) or PD-L1 status (p = 0.214). In a subset analysis of patients with metastatic NSCLC, there was also no correlation between the total number of mutations and overall survival (p = 0.821). Conclusions: In our study, we determined that there was a positive correlation between TMB and higher number of mutations, though the number of mutations did not correlate with PD-L1 status or overall survival. As TMB is associated with higher immunogenic responses, this data may have future therapeutic implications. Additional investigation of the most frequent mutations is ongoing.