KRAS-mutated non-small cell lung cancer (NSCLC) in South India: Real-world genomic landscape, treatment patterns, and outcomes

ABSTRACT Background: KRAS mutated metastatic non-small cell lung cancer (NSCLC) is characterized by clinical and genomic heterogeneity. There is paucity of data on this subtype from low- and middle- income countries (LMICs), where emerging therapeutic options are of limited accessibility. Methods: We conducted a retrospective study at Regional Cancer Centre, Kerala, India between June 2021 and June 2025. 220 metastatic NSCLC cases underwent NGS; 57/220 (26%) were KRAS mutated and formed the descriptive cohort. After exclusions, 47 were evaluable for response and survival, analysed using Kaplan Meier and log rank tests (two-sided P ≤ 0.05). Results: Median age was 61 years; 73% were men; 63% had a smoking history. The most KRAS mutations were G12C (37%), G12D (19%), G12A (16%), and G12V (12%). Co-mutations occurred in 53% ( TP53 35%, PIK3CA 11%). 28% patients were PD-L1 positive. First-line therapy was predominantly platinum doublet (83%); with added bevacizumab in 16% and an immune checkpoint inhibitor (ICI) in 7%. At a median follow-up of 19.9 months, median progression-free survival (PFS) was 9.6 months (95% CI: 7.47–13.23), and median overall survival (OS) was 12.07 months (95% CI: 9.10–16.33). G12C mutation conferred improved OS whereas, Eastern Co-operative Oncology Group Performance Status (ECOG PS) ≥2 and TP53 co-mutation predicted inferior OS. Anti-vascular endothelial growth factor (VEGF) exposure showed a trend towards improved OS. Conclusions: In this South Indian cohort, KRAS mutations were heterogeneous, G12C-predominant. Overall survival was modest, reflecting limited access to immunotherapy and KRAS inhibitors. G12C subtype had improved outcomes while TP53 co-mutation had poorer outcomes. These findings support broader molecular testing, better therapy access, and prospective validation in LMICs.