Background

Kirsten rat sarcoma viral oncogene (KRAS) G12C mutation occurs in about 4% of colorectal cancers (CRCs). Recently, KRAS G12C was identified to be a potential drug target and predictor of response to the novel on AMG510 target treatment. We described the clinicopathologic features and prognosis of KRAS G12C-mutated metastatic CRCs compared to other KRAS mutation.

Patients and Methods

Clinicopathologic features and outcome data of KRAS-mutated metastatic CRC (mCRC) patients referred to 3 Italian oncology units from January 2010 to December 2018 were collected. A cohort of KRAS-mutant mCRC patients referred to the Department of Medical Oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy) within the same time frame was included as external validation.

Results

A total of 839 KRAS-mutated mCRC cases were included in the main patient population. A total of 145 patients (17%) had KRAS G12C mutation. Our analyses showed that patients harboring KRAS G12C mutation were more likely to be men and to present lung and liver metastases, and were less likely to have peritoneal spread. KRAS G12C mutation was associated with shorter overall survival compared to other KRAS mutations (hazard ratio, 1.32; 95% confidence interval, 1.07-1.63; P = .009). Such results were confirmed in the external validation cohort.

Conclusion

The knowledge of the distinctive traits of KRAS G12C-mutated CRC patients is crucial to future translational research studies, clinical trial design, and proper interpretation of results.

中文翻译：

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KRAS G12C 转移性结直肠癌：新出现的目标人群的特定特征。

背景

Kirsten 大鼠肉瘤病毒癌基因 ( KRAS ) G12C 突变发生在约 4% 的结直肠癌 (CRC) 中。最近，KRAS G12C 被确定为潜在的药物靶点和对 AMG510 靶点治疗新反应的预测因子。我们描述了与其他KRAS突变相比，KRAS G12C 突变的转移性 CRC的临床病理特征和预后。

患者和方法

收集了 2010 年 1 月至 2018 年 12 月转诊至 3 个意大利肿瘤科的KRAS突变转移性 CRC (mCRC) 患者的临床病理特征和结果数据。在同一时间范围内，转诊到米兰（意大利）的 Fondazione IRCCS Istituto Nazionale dei Tumori 肿瘤科的一组KRAS突变 mCRC 患者被纳入作为外部验证。

结果

主要患者群体中包括总共 839例KRAS突变的 mCRC 病例。共有 145 名患者（17%）具有KRAS G12C 突变。我们的分析表明，携带KRAS G12C 突变的患者更可能是男性，并且出现肺和肝转移，并且不太可能发生腹膜扩散。与其他KRAS突变相比，KRAS G12C 突变与较短的总生存期相关（风险比，1.32；95% 置信区间，1.07-1.63；P  = .009 ）。这样的结果在外部验证队列中得到证实。

结论

了解KRAS G12C 突变 CRC 患者的独特特征对于未来的转化研究、临床试验设计和正确解释结果至关重要。