The Prognostic Impact of KRAS G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study

The oncologist

article

Keigo Chida¹  Daisuke Kotani¹  Toshiki Masuishi³  Takeshi Kawakami⁴  Yasuyuki Kawamoto⁵  Kyoko Kato³  Kunihiro Fushiki⁴  Kentaro Sawada⁵  Ryosuke Kumanishi³  Hiromichi Shirasu⁴  Yuki Matsubara³  Satoshi Yuki⁵  Yoshito Komatsu⁵  Kentaro Yamazaki⁴  Takayuki Yoshino¹ 

[1] Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East;Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine;Department of Clinical Oncology, Aichi Cancer Center Hospital;Division of Gastrointestinal Oncology, Shizuoka Cancer Center;Department of Gastroenterology and Hepatology, Hokkaido University Hospital;Department of Medical Oncology, Kushiro Rosai Hospital

关键词: KRAS;    G12C;    Colorectal cancer;    Chemotherapy;    Prognosis;   

DOI  :  10.1002/onco.13870

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background KRAS is one of the most frequently mutated oncogenes in colorectal cancer (CRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising activities for corresponding advanced solid tumors, including metastatic CRC (mCRC). However, the prognostic impact of the KRAS G12C mutation remains unclear in patients with mCRC. Materials and Methods We retrospectively reviewed medical records of patients with mCRC who received first-line chemotherapy between January 2005 and December 2017 at four large oncology facilities in Japan. Survival outcomes were compared between patients with KRAS G12C and those with non-G12C mutations. Results Among 2,457 patients with mCRC, 1,632 met selection criteria, and of these, 696 had KRAS exon 2 mutations, including 45 with KRAS G12C mutation tumors. Patient characteristics were not significantly different between the KRAS G12C and non-G12C groups. At a median follow-up of 64.8 months, patients with the KRAS G12C mutation showed significantly shorter first-line progression-free survival (PFS; median, 9.4 vs. 10.8 months; p  = .015) and overall survival (OS; median, 21.1 vs. 27.3 months; p  = .015) than those with non-G12C mutations. Multivariate analysis also showed that KRAS G12C mutation was significantly associated with shorter PFS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.04–1.96, p  = .030) and OS (HR, 1.42; 95% CI, 1.01–2.00; p  = .044). Conclusion We demonstrate that, compared with non-G12C mutations, KRAS G12C mutation is significantly correlated with shorter first-line PFS and OS. These findings indicate the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC. Implications for Practice Among patients with KRAS exon 2 mutated metastatic colorectal cancer (mCRC), median progression-free survival (PFS) and overall survival (OS) were 9.4 and 21.1 months, respectively, for G12C mutation and 10.8 and 27.3 months, respectively, for patients with non-G12C mutations, indicating significantly shorter PFS (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08–2.01; p  = .015) and OS (HR, 1.50; 95% CI, 1.08–2.08; p  = .015) in patients with G12C mutation than in those with non-G12C mutations. Furthermore, multivariate analysis showed that KRAS G12C mutation was independently associated with shorter first-line PFS and OS. Thus, these findings underscore the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.

【 授权许可】

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