Assessing the significance of KRAS G12C mutation: Clinicopathologic features, treatments, and survival outcomes in a real-world KRAS mutant non-small cell lung cancer cohort.

e19324 Background: KRASG12C mutations are present in 15% of non-small cell lung cancer (NSCLC) and have recently been shown to confer sensitivity to KRAS(G12C) inhibitors. This study aims to assess the clinical features and outcomes with KRASG12C mutant NSCLC in a real-world setting. Methods: Patients enrolled in an Australian prospective cohort study, Thoracic Malignancies Cohort (TMC), between July 2012 to October 2019 with metastatic or recurrent non-squamous NSCLC, with available KRAS test results, and without EGFR, ALK, or ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival was compared for KRAS wildtype ( KRASWT) and KRAS mutated ( KRASmut) patients, and between KRAS G12C ( KRASG12C) and other ( KRASother) mutations. Results: Of 1386 patients with non squamous NSCLC, 1040 were excluded for: non metastatic or recurrent (526); KRAS not tested (356); ALK, EGFR or ROS1 positive (154); duplicate (4). Of 346 patients analysed, 202 (58%) were KRASWT and 144 (42%) were KRASmut, of whom 65 (45%) were KRASG12C. 100% of pts with KRASG12C were smokers, compared to 92% of KRASother and 83% of KRASWT. The prevalence of brain metastases over entire follow-up period was similar between KRASmut and KRASWT (33% vs 40%, p = 0.17), and KRASG12C and KRASother (40% vs 41%, p = 0.74). Likewise, there was no difference in the proportion of patients receiving one or multiple lines of systemic therapy. Overall survival (OS) was also similar between KRASmut and KRASWT (p = 0.54), and KRASG12C and KRASother (p = 0.39). Conclusions: In this real-world prospective cohort, patients had comparable clinical features regardless of having a KRASmut, KRASG12C or KRASother mutation, or being KRASWT . Treatment and survival were also similar between groups. While not prognostic, KRASG12C may be an important predictive biomarker as promising KRAS G12C covalent inhibitors continue to be developed.