Outcomes of advanced Non-Small Cell Lung Cancer patients From the IFCT Biomarkers France study by KRAS Mutation Subtypes

ABSTRACT Introduction Kirsten Rat Sarcoma viral oncogene homolog (KRAS) mutations are detected in 20–30% of non-small cell lung cancers (NSCLC). However, KRAS mutation subtypes may differently influence advanced NSCLC patient outcomes. Methods In the Biomarkers France study, 4,894 (26.2%) KRAS mutations were detected in 4,634 patients among the 17,664 NSCLC enrolled. Survival and treatment data on non-curative Stage III–IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival (PFS) and overall survival (OS) were analyzed according to the KRAS mutations subtype. Results Over 95% of the KRAS-mutated patients were smokers or former smokers of Caucasian origin (99.5%) with adenocarcinoma as predominant histology. The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had a transition mutation, and 68.2% a transversion mutation. G12D and transition mutations were predominant in never smokers. The median OS for KRAS-mutated NSCLC patients was 8.1 months (95% CI: 7.5–9.5), without significant differences according to the different KRAS subtypes mutations. The median PFS was 4.6 months (95%CI: 4.2–5.1) for first-line treatment and 4.8 months (95%CI: 4.3–6.8) for second-line, without significant differences according to the different KRAS subtypes mutations. Conclusions KRAS mutation subtypes influenced neither treatment responses nor outcomes. The G12C mutation was detected in 41.5% of patients, which are now eligible for potent and specific G12C inhibitors.