Identifying genetic biomarkers predicting response to immunotherapy in non-small cell lung cancer

Abstract

Background Immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) in the last decade. However, not all patients respond to immunotherapy and current biomarkers used for patient selection are not optimal. Therefore, new and better biomarkers are urgently needed. This study aims to find genetic biomarkers predicting immunotherapy response in NSCLC patients. Method Tumor DNA was sequenced for 44 NSCLC patients undergoing immunotherapy. Variants in 597 genes from GATC Biotech’s OncoPanel All-in-One were assessed in silico and the genetic landscape was characterized. Kaplan-Meier analysis using log-rank test was used to assess the association of the top frequently mutated genes with survival and Cox regression was used to adjust for patients-related factors. Association with immunotherapy response was evaluated using Pearson’s chi-squared test. Results Patients with KRAS mutation and KRAS/LRP1B co-mutation were identified to be associated with prolonged survival (p=0.033 and p=0.022) and a trend for preferable immunotherapy response was observed. Patients with a low number of variants classified as pathogenic, likely pathogenic and ”VUS+” was also found to be associated with survival (p=0.032) and were more likely to be responders of immunotherapy compared to patients with a high number of these variants (p=0.020). Conclusion This project has further supported the role of KRAS as a potential predictive biomarker of immunotherapy response and has provided evidence for the KRAS/LRP1B co-mutation and the number of classified variants as potential biomarkers. Further studies including more patients may find additional results supporting the presented findings.