Real-world treatment pattern and clinical outcomes in Chinese NSCLC patients with KRAS G12C mutation
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Updated: Oct 31, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Lan Shen1, Yibo Gao2, Zhengbo Song3
1Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20030, China.
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
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.
