Introduction: Mutations in the KRAS gene are the most common driver oncogenes present in lung adenocarcinomas. We analyzed the largest multi‐institutional database available containing patients with metastatic KRAS‐mutant lung adenocarcinomas. Methods: The Lung Cancer Mutation Consortium (LCMC) is a multi‐institutional collaboration to study the genomic characteristics of lung adenocarcinomas, treat them with genomically directed therapeutic approaches, and assess their outcomes. Since its inception in 2009, the LCMC has enrolled more than 1900 patients and has performed pretreatment, multiplexed, molecular characterization along with collecting clinical data. We evaluated the characteristics of patients with KRAS mutation in the LCMC and the association with overall survival. Results: Data from 1655 patients with metastatic lung adenocarcinomas were analyzed. Four hundred fifty (27%) patients had a KRAS mutation, 58% were female, 93% were smokers, and there was a median age of 65 years. Main KRAS subtypes were: G12C 39%; and G12D and G12V at 18% each. Among patients with KRAS mutation, G12D had a higher proportion of never‐smokers (22%, p < 0.001). Patients with KRAS‐mutant tumors had a trend toward shorter median survival compared to all others in the series (1.96 versus 2.22; P = 0.08) and lower 2‐year survival rate (49% [95% confidence interval: 44%–54%] and 55% [95% confidence interval: 52%–58%], respectively). Conclusions: In the LCMC study, 27% of lung adenocarcinomas patients harbored a KRAS mutation and up to one‐third of them had another oncogenic driver. Patients with both KRAS and STK11 mutations had a significantly inferior clinical outcome.

中文翻译：

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转移性 KRAS 突变肺腺癌患者的特征和结果：肺癌突变联盟的经验

简介： KRAS 基因突变是肺腺癌中最常见的驱动癌基因。我们分析了最大的多机构数据库，其中包含转移性 KRAS 突变型肺腺癌患者。方法：肺癌突变联盟 (LCMC) 是一个多机构合作机构，旨在研究肺腺癌的基因组特征，使用基因组定向治疗方法对其进行治疗，并评估其结果。自 2009 年成立以来，LCMC 已招募了 1900 多名患者，并进行了预处理、多路复用、分子表征以及收集临床数据。我们评估了 LCMC 中 KRAS 突变患者的特征以及与总生存期的关联。结果：分析了 1655 名转移性肺腺癌患者的数据。四百五十 (27%) 名患者有 KRAS 突变，58% 为女性，93% 为吸烟者，中位年龄为 65 岁。主要 KRAS 亚型为：G12C 39%；G12D 和 G12V 各为 18%。在 KRAS 突变的患者中，G12D 的从不吸烟者比例较高（22%，p < 0.001）。与该系列中的所有其他患者相比，KRAS 突变肿瘤患者的中位生存期有缩短的趋势（1.96 对 2.22；P = 0.08）和较低的 2 年生存率（49% [95% 置信区间：44%–54% ] 和 55% [95% 置信区间：分别为 52%–58%]）。结论：在 LCMC 研究中，27% 的肺腺癌患者携带 KRAS 突变，其中多达三分之一具有另一种致癌驱动因素。