Liu et al. Biomarker Research (2020) 8:22
Clinical characteristics and prognostic value of the KRAS G12C mutation in Chinese nonsmall cell lung cancer patients
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https://biomarkerres.biomedcentral.com/track/pdf/10.1186/s40364-020-00199-z
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https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-020-00199-z
ABSTRACT
BACKGROUND: The KRAS mutation is the second most common genetic variant in Chinese non-small cell lung cancer (NSCLC) patients. At the 2019th World Conference of Lung Cancer, the KRAS G12C-specific inhibitor AMG510 showed promising results in the phase I clinical trial. However, the frequency, clinical characteristics, and prognostic significance of the KRAS G12C mutation in Chinese NSCLC patients are rarely reported.
METHODS: Next-generation sequencing was used to confirm the KRAS mutation status in 40,804 NSCLC patients from multiple centers (mCohort). Survival data were collected retrospectively from 1456 patients at one of the centers, the Guangdong Lung Cancer Institute (iCohort).
RESULTS:
中国人，非小细胞肺癌，9.8%有KRAS突变，其中，29.5%为KRAS G12C亚型。男性和吸烟者更多见。KRAS和KRAS G12C亚型均为不良预后的指标。
In the mCohort, 3998 patients (9.8%) were confirmed to harbor a KRAS mutation, of whom 1179 (29.5%) had the G12C subtype. In the iCohort, 130 NSCLC patients (8.9%) had a KRAS mutation and 42 (32.3%) had the G12C subtype. The G12C subgroup included more male patients (85.2% vs 67.4%, P < 0.0001) and more smokers (76.2% vs 53.4%, P = 0.02) than did the non-G12C subgroup. Both the KRAS mutation group and KRAS G12C mutation subgroup were associated with a shorter median overall survival (OS) than wildtype tumors (15.1 vs 26.7 months, hazard ratio [HR] KRAS = 1.50, P = 0.002; 18.3 vs 26.7 months, HR G12C = 1.66, P = 0.007). In Cox regression analysis, smoking (HR = 1.39, P = 0.05) and stage IV disease (HR = 2.72, P < 0.001) remained as independent predictors of shorter OS. Both the KRAS mutation (HR = 1.30, P = 0.07) and KRAS G12C mutation (HR = 1.47, P = 0.07) reached borderline significance.
CONCLUSIONS: In the largest sample used thus for, our study found that approximately 10% of Chinese NSCLC patients had KRAS mutations. Of these, nearly 30% harbored the KRAS G12C mutation subtype, which was most common in male smokers. The KRAS G12C mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which could potentially be improved by G12C-specific inhibitors in the future.
真实世界KRAS G12C 突变者的治疗及生存分析
澳大利亚Peter MacCallum 癌 症中心Cui 等报告， 携带KRAS 突变型和KRAS 野生型、KRAS G12C 型和KRAS 其他基因型非小 细胞肺癌（NSCLC）患者的临床 特征、治疗情况及生存期均相似， KRAS G12C 并非预后标志物， 但或可作为预测标志物。（Lung Cancer. 2020 年6 月26 日在线版 doi: 10.1016/j.lungcan.2020.06.030） NSCLC 中KRAS 突变占
20%~30%，通常认为无相应的靶向 药物可用。虽然KRAS G12C 突变 对KRAS G12C 共价抑制剂敏感， 但其预后作用尚待明确。
为了在真实世界的NSCLC KRAS G12C 患者中评估脑转移的 患病率、临床特征及结局，该项 前瞻性胸部恶性肿瘤队列（TMC） 研究于2012 年7 月至2019 年10 月入组复发/ 转移性NSCLC 患者， 有KRAS 结果且不携带EGFR/ ALK/ROS1 基因异常， 自TMC 队列和患者病案中提取数据，对 比KRAS 野生型、KRAS 突变型、KRAS G12C 型和KRAS 其他基因 型患者的临床病理特征、治疗情 况及总生存期（OS）。
结果显示，筛选1386 例患者， 排除1040 例；其中非转移/ 非复 发性526 例，KRAS 状态未知356 例，ALK/EGFR/ROS1 阳性154 例， 复制型4 例。346 例被纳入分析， 包括KRAS 突变型144 例（42%）， 其中KRAS G12C 型65 例（45%）。 所有KRAS G12C 型患者均为吸烟 活跃者或曾吸烟者，而KRAS 其 他基因型和KRAS 野生型中则分 别为92% 和83%。
随访中，KRAS 突变型和 KRAS 野生型患者的脑转移患病率 相近，分别为33% 和40%（P=0.17）， KRAS G12C 型和KRAS 其他基因 型中分别为40% 和41%（P=0.774）。 一线或多线系统治疗患者的比例相 近。KRAS 突变型和KRAS 野生型 患者的OS 相近（P=0.54），KRAS G12C 型和KRAS 其他基因型中也 相近（P=0.39）。
