Department of Oncology, Veneto Institute of Oncology IOV IRCCS, Padua, Italy.
Department of Oncology, Veneto Institute of Oncology IOV IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Clin Colorectal Cancer. 2020 Sep;19(3):219-225. doi: 10.1016/j.clcc.2020.04.009. Epub 2020 May 12.
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.
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.
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.
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.
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 被确定为一种潜在的药物靶点和对新型 AMG510 靶向治疗反应的预测因子。我们描述了 KRAS G12C 突变转移性 CRC 与其他 KRAS 突变相比的临床病理特征和预后。
收集了 2010 年 1 月至 2018 年 12 月期间向意大利 3 个肿瘤学单位转诊的 KRAS 突变转移性 CRC (mCRC) 患者的临床病理特征和结局数据。在同一时间段内，还纳入了米兰 Fondazione IRCCS Istituto Nazionale dei Tumori 医学肿瘤学系转诊的 KRAS 突变 mCRC 患者队列作为外部验证。
主要患者人群中共有 839 例 KRAS 突变 mCRC 病例。共有 145 例患者（17%）存在 KRAS G12C 突变。我们的分析表明，携带 KRAS G12C 突变的患者更可能为男性，且更易发生肺和肝转移，而腹膜转移的可能性较小。与其他 KRAS 突变相比，KRAS G12C 突变与总生存期缩短相关（危险比，1.32；95%置信区间，1.07-1.63；P=0.009）。这些结果在外部验证队列中得到了证实。
了解 KRAS G12C 突变 CRC 患者的独特特征对于未来的转化研究、临床试验设计和结果的正确解释至关重要。
