P59.12 KRAS Mutation Subtypes in Non-Small Cell Lung Cancer and Clinical Outcomes: A Single Centre Experience

Abstract

KRAS is a common molecular driver in lung adenocarcinoma. KRAS subtypes can be grouped into transversion mutations (exchange of a purine for a pyrimidine bases or vice versa) such as KRAS G12C/G12V and transition mutations (interchange of a purine for another purine or interchange of a pyrimidine for another pyrimidine) such as KRAS G12D. This study assessed the efficacy of treatment and CNS prevalence across different subtypes of KRAS mutant NSCLC. Retrospective review of routine, clinical, molecular testing in NSCLC at a single centre over an 8-year period was performed. Clinicopathological information was obtained from medical records in patients with a KRAS mutation. Overall survival (OS) and Progression free survival (PFS) from diagnosis and OS following immunotherapy (iOS; in any line of treatment) were assessed using the Kaplan-Meier method and differences in survival were assessed by log-rank test. The difference between light/non-smokers and heavy smokers was assessed by Pearsons chi squared test. The presence of CNS disease was assessed by multivariate, nominal, logistic regression. From 1054 assessed 272 (25.8%) were found to be KRAS mutant with 72 patients receiving immunotherapy for stage III/IV disease. Immunotherapy included any PD(L)1, CTLA4 or investigational immunotherapy. KRAS G12C was found in 103 patients (38%), KRAS G12D in 48 patients (18%) and KRAS G12V in 53 patients (19%) (Figure 1). There was no difference in the presence of CNS disease across KRAS subtypes (p = 0.149). Non/light smokers were more likely to have a transition KRAS mutation than transversion mutation (p < 0.001). There was no difference across specific KRAS mutation subtype for PFS, OS or iOS. Transversion KRAS mutations had better iOS than transition KRAS mutations (Figure 2). Transversion KRAS mutations may predict for improved OS following immunotherapy but requires validation in a larger prospective cohort. Retrospective analysis of this cohort by PDL1 is underway.