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

作者：Keigo Chida, Daisuke Kotani, Toshiki Masuishi, Takeshi Kawakami, Yasuyuki Kawamoto, Kyoko Kato, Kunihiro Fushiki, Kentaro Sawada, Ryosuke Kumanishi, Hiromichi Shirasu, Yuki Matsubara, Satoshi Yuki, Yoshito Komatsu, Kentaro Yamazaki, Takayuki Yoshino · 发表于：The Oncologist · 年份：2021 · DOI：10.1002/onco.13870 · 被引用次数：52 · 研究领域：Colorectal Cancer Treatments and Studies、Advanced Breast Cancer Therapies、Cancer Genomics and Diagnostics

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 mu...