随着G12C抑制剂作为KRAS G12C突变NSCLC的第二线治疗获得批准，并且有关靶向KRAS的研究不断扩大，了解KRAS G12C在当前一线治疗中的预后意义至关重要。我们在一线（化学）免疫治疗环境中，比较了在晚期IV期KRAS G12C突变NSCLC患者与KRAS非G12C突变的患者之间的总生存期（OS）。本研究使用荷兰癌症登记处的真实世界数据，选取了2019年至2020年被诊断出晚期IV期KRAS突变肺腺癌并接受一线（化学）免疫治疗的患者。主要结果是总生存期。从28,120例登记的肺癌患者中，选择了1185例KRAS突变患者，其中494例为KRAS G12C突变。KRAS G12C突变患者的中位OS为15.5个月（95%置信区间[CI]：13.6-18.4），而KRAS非G12C突变患者的中位OS为14.0个月（95%CI：11.2-15.7）（p = 0.67）。在多变量分析中，KRAS亚型与OS无关（风险比= 0.95，95%CI：0.82-1.10）。对于PD-L1在0%到49%之间并接受化疗免疫治疗的亚组，G12C和非G12C的中位OS分别为13.3个月（95%CI：10.5-15.2）和9.8个月（95%CI：8.6-11.3）（p = 0.48）。对于PD-L1大于或等于50%并接受单免疫治疗的亚组，G12C和非G12C的中位OS分别为22.0个月（95%CI：18.4-27.3）和18.9个月（95%CI：14.9-25.2）（p = 0.36）。在接受一线（化学）免疫治疗的KRAS突变晚期IV期NSCLC患者中，KRAS亚型（G12C与非G12C）对OS没有影响。©2023年作者。

With the approval of G12C inhibitors as the second line of treatment for KRAS G12C-mutated NSCLC, and the expanding research regarding targeting KRAS, it is key to understand the prognostic implication of KRAS G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV KRAS G12C-mutated NSCLC to those with a KRAS non-G12C mutation in a first-line setting of (chemo)immunotherapy.This nationwide population-based study used real-world data from The Netherlands Cancer Registry. We selected patients with stage IV KRAS-mutated lung adenocarcinoma diagnosed in 2019 to 2020 who received first-line (chemo-)immunotherapy. Primary outcome was OS.From 28,120 registered patients with lung cancer, 1185 were selected with a KRAS mutation, of which 494 had a KRAS G12C mutation. Median OS was 15.5 months (95% confidence interval [CI]: 13.6-18.4) for KRAS G12C versus 14.0 months (95% CI:11.2-15.7) for KRAS non-G12C (p = 0.67). In multivariable analysis, KRAS subtype was not associated with OS (hazard ratio = 0.95, 95% CI: 0.82-1.10). For the subgroup with programmed death-ligand 1 at 0% to 49% who received chemoimmunotherapy, median OS was 13.3 months (95% CI: 10.5-15.2) for G12C and 9.8 months (95% CI: 8.6-11.3) for non-G12C (p = 0.48). For the subgroup with programmed death-ligand 1 more than or equal to 50% who received monoimmunotherapy, the median OS was 22.0 months (95% CI: 18.4-27.3) for G12C and 18.9 months (95% CI: 14.9-25.2) for non-G12C (p = 0.36).There was no influence of KRAS subtype (G12C versus non-G12C) on OS in patients with KRAS-mutated stage IV NSCLC treated with first-line (chemo)immunotherapy.© 2023 The Authors.