Prognostic Role of KRAS G12C Mutation in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

KRAS G12C mutation (mKRAS G12C) is the most frequent KRAS point mutation in non-small cell lung cancer (NSCLC) and has been proven to be a predictive biomarker for direct KRAS G12C inhibitors in advanced solid cancers. We sought to determine the prognostic significance of mKRAS G12C in patients with NSCLC using the meta-analytic approach. A protocol is registered at the International Prospective Register for systematic reviews (CRD42022345868). PubMed, EMBASE, The Cochrane Library, and Clinicaltrials.gov.in were searched for prospective or retrospective studies reporting survival data for tumors with mKRAS G12C compared with either other KRAS mutations or wild-type KRAS (KRAS-WT). The hazard ratios (HRs) for overall survival (OS) or Disease-free survival (DFS) of tumors were pooled according to fixed or random-effects models. Sixteen studies enrolling 10,153 participants were included in the final analysis. mKRAS G12C tumors had poor OS [HR, 1.42; 95% CI, 1.10–1.84, p = 0.007] but similar DFS [HR 2.36, 95% CI 0.64–8.16] compared to KRAS-WT tumors. Compared to other KRAS mutations, mKRAS G12C tumors had poor DFS [HR, 1.49; 95% CI, 1.07–2.09, p < 0.0001] but similar OS [HR, 1.03; 95% CI, 0.84–1.26]. Compared to other KRAS mutations, high PD-L1 expression (>50%) [OR 1.37 95% CI 1.11–1.70, p = 0.004] was associated with mKRAS G12C tumors. mKRAS G12C is a promising prognostic factor for patients with NSCLC, negatively impacting survival. Prevailing significant heterogeneity and selection bias might reduce the validity of these findings. Concomitant high PD-L1 expression in these tumors opens doors for exciting therapeutic potential.