KRAS G12C Metastatic Colorectal Cancer: Specific Features of a New Emerging Target Population

• Published in: Clinical colorectal cancer 2020-09, Vol.19 (3), p.219-225
• Main Authors: Schirripa, Marta, Nappo, Floriana, Cremolini, Chiara, Salvatore, Lisa, Rossini, Daniele, Bensi, Maria, Businello, Gianluca, Pietrantonio, Filippo, Randon, Giovanni, Fucà, Giovanni, Boccaccino, Alessandra, Bergamo, Francesca, Lonardi, Sara, Dei Tos, Angelo Paolo, Fassan, Matteo, Loupakis, Fotios
• Format: Article
• Language: English
• Subjects: AMG510; G12C; KRAS mutation; Metastatic colorectal cancer; Prognosis
• ISSN: 1533-0028; 1938-0674
• DOI: 10.1016/j.clcc.2020.04.009

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 rat sarcoma viral oncogene (KRAS) G12C was identified to be a drug target and a predictor of response to the novel AMG510 drug. We showed that KRAS G12C-mutated colorectal cancer has specific clinicopathologic features and worse outcome compared to other KRAS-mutated cases. The knowledge of such distinctive traits of KRAS G12C mutations might be crucial to future translational research studies and clinical trial design.