Real-world treatment pattern and clinical outcomes in Chinese NSCLC patients with KRAS G12C mutation

To establish a historical benchmark by describing the treatment patterns and clinical outcomes of Chinese patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) in the real world, prior to the widespread availability of KRAS G12C inhibitors. This retrospective cohort study utilized electronic medical records from four tertiary hospitals in China (January 2015 to March 2023). Inclusion criteria: age ≥ 18 years, histologically confirmed locally advanced/metastatic NSCLC, KRAS G12C mutation, receipt of ≥1st line treatment, and ≥ 6 months of follow-up. The primary endpoint was the proportion of different regimens used per line of therapy. Secondary endpoints included real-world overall response rate (rwORR), progression-free survival (rwPFS). Multivariable COX regression and treatment era analyses (<2020 vs. ≥ 2020) were additionally conducted. Among 244 included patients (93.85% male, 74.57% were smokers), first-line treatment comprised chemotherapy-based (38.70%), immune-based (10.87%), chemo-immunotherapy (50.00%). The first-line rwORR was 19.1% (chemotherapy), 20% (immune-based), and 26.96% (chemo-immunotherapy), respectively. Median rwPFS was 8.25, 21.00, 16.00 months, respectively. In multivariable Cox analysis, compared to chemotherapy, chemo-immunotherapy (HR 0.39, 95% CI 0.24–0.63, p < 0.001) and immune-based therapy (HR 0.34, 95% CI 0.15–0.80, p = 0.014) showed independent rwPFS benefit. However, the immune-based group was highly enriched for PD-L1 ≥ 50% (52.00% vs. 26.96% in the overall first-line cohort). STK11 mutation was a strong independent predictor of poor rwPFS (HR 5.53, 95% CI 2.77–11.05, p < 0.001). Treatment patterns shifted significantly, with first-line chemo-immunotherapy increasing from 24.64% (< 2020) to 60.87% (≥ 2020). This real-world study provides a comprehensive characterization of the clinical management and outcomes of KRAS G12C-mutated NSCLC in China in the pre-KRAS G12C inhibitor treatment era. First-line chemo-immunotherapy provides independent survival benefit over chemotherapy, with immune monotherapy reserved for carefully selected PD-L1 high cases. STK11 co-mutation predicts extremely poor outcomes (median PFS 3.75 months), representing an unmet clinical need. This study provides an essential historical reference for quantifying their real-world clinical impact.