Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer

BACKGROUND: KRAS mutations are found in 20-30 % of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRASG12C mutation confers sensitivity to KRASG12C covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRASG12C NSCLC in a real-world setting. METHODS: Patients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRASWT) and KRAS mutated (KRASmut); and KRASG12C and other (KRASother) mutations. RESULTS: Of 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 %) were KRASmut, of whom 65 (45 %) were KRASG12C. All patients with KRASG12C were active or ex-smokers, compared to 92 % of KRASother and 83 % of KRASWT. The prevalence of brain metastases during follow-up was similar between KRASmut and KRASWT (33 % vs 40 %, p = 0.17), and KRASG12C and KRASother (40 % vs 41 %, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRASmut and KRASWT (p = 0.54), and KRASG12C and KRASother (p = 0.39). CONCLUSION: Patients with KRASmut and KRASWT, and KRASG12C and KRASother NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRASG12C may be an important predictive biomarker as promising KRASG12C covalent inhibitors continue to be developed