免疫治疗对KRAS G12C突变与非G12C突变非小细胞肺癌的临床结局：一项多中心真实世界研究
Clinical outcomes of KRAS G12C versus non-G12C mutant NSCLC treated with immunotherapy: a multicentre real-world study.
作者
作者单位
- Medical Oncology, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain.
- Medical Oncology, Hospital Universitari Son Espases, Palma de Mallorca, Spain.
- Medical Oncology, Hospital Universitario de Navarra, Navarra, Spain.
- Department of Pathology, Hospital Universitari Son Espases, Palma de Mallorca, Spain.
- Cancer Research Program, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain.
- Department of Pathology, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain.
- Medical Oncology, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain. Electronic address: earriola@parcdesalutmar.cat.
摘要
中文
KRAS是NSCLC中最异质且最常见的致癌驱动基因。KRAS等位基因和共突变塑造肿瘤微环境，可能影响对免疫检查点抑制剂（ICI）的获益。本研究旨在评估KRAS突变模式、其与临床病理特征的相关性及其与ICI结局的关联。我们开展了一项多中心回顾性分析，纳入了接受ICI治疗的晚期KRAS突变NSCLC患者。收集临床、病理和分子数据，包括KRAS突变类型（G12C与非G12C）、关键共突变和PD-L1表达。这些变量与临床结局相关。生存结局采用Kaplan-Meier估计和多变量Cox回归模型分析。共评估了198例KRAS突变NSCLC患者，其中49.5%携带G12C突变。总体而言，81%的患者接受了一线ICI，包括单药或联合化疗。中位随访48个月后，G12C病例的中位总生存期（OS）显著更长（15 vs 9个月；HR 0.71；p=0.031）。多变量分析显示，G12C突变与OS改善相关，同时与良好体能状态和无中枢神经系统（CNS）转移相关。在这个回顾性真实世界队列中，KRAS突变亚型与ICI结局（尤其是OS）的差异相关。这些发现应视为产生假说，并需要在分子特征明确的队列中进行前瞻性验证。
English
KRAS is the most heterogeneous and frequent oncogenic driver in non-small cell lung cancer (NSCLC). KRAS alleles and co-mutations shape the tumour microenvironment, potentially influencing benefit from immune checkpoint inhibitors (ICI). The aim of our study was to evaluate the patterns of KRAS mutations, their correlation with clinical and pathological features and their association with ICI outcomes. We conducted a multicentre retrospective analysis of patients with advanced KRAS-mutant NSCLC treated with ICI. Clinical, pathological and molecular data were collected, including KRAS mutation type (G12C vs non-G12C), key co-mutations and PD-L1 expression. These variables were correlated with clinical outcomes. Survival outcomes were analysed using Kaplan-Meier estimates and multivariate Cox regression models. A total of 198 patients with KRAS mutant NSCLC were evaluated, with 49.5% carrying a G12C mutation. Overall, 81% of patients received first-line ICI, either as monotherapy or combined with chemotherapy. After a median follow-up of 48 months, G12C cases showed significantly longer median overall survival (OS) (15 vs 9 months; HR 0.71; p = 0.031). Multivariate analysis indicated that G12C mutations correlated with improved OS, as well as good performance status and absence of central nervous system (CNS) metastases. In this retrospective real-world cohort, KRAS mutation subtype was associated with differences in ICI outcomes, particularly OS. These findings should be considered hypothesis-generating and warrant prospective validation in molecularly characterized cohorts.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区