Clinical and prognostic features of patients with detailed RAS/BRAF-mutant colorectal cancer in Japan

Abstract

Background: RAS/BRAF^V600E mutations are the most remarkable oncogenic driver mutations in colorectal cancer (CRC) and play an important role in treatment selection. No data are available regarding the clinical and prognostic features of patients with detailed RAS/BRAF^V600E-mutant metastatic CRC (mCRC) in Japan.

Methods: A total of 152 chemotherapy-naïve patients with mCRC were included in this study between August 2018 and July 2019. Tumor samples were collected, and RAS/BRAF^V600E status was investigated. RAS/BRAF^V600E status was examined using a MEBGEN RASKET-B kit and polymerase chain reaction reverse sequence-specific oligonucleotide method.

Results: RAS/BRAF^V600E mutations were detected in 54% of cases (KRAS codon 12, 26%; KRAS codon 13, 17%; KRAS non-Exon2, 5%; NRAS, 5%; and BRAF^V600E, 7%). BRAF^V600E-mutant CRC mainly existed in the right colon, whereas KRAS non-Exon2 and NRAS-mutant CRC was predominantly present in the left colon. KRAS non-Exon2 and NRAS-mutant CRC were associated with shorter survival time than RAS wild-type CRC (hazard ratio [HR], 2.26; 95% confidence interval [CI], 0.64-8.03; p = 0.19; HR, 2.42; 95% CI, 0.68-8.61; p = 0.16) and significantly shorter overall survival than KRAS Exon2-mutant CRC (HR, 3.88; 95% CI, 0.92-16.3; p = 0.04; HR, 4.80; 95% CI, 1.14-20.2; p = 0.02).

Conclusions: In our multicenter study, the findings elucidated the clinical and prognostic features of patients with detailed RAS/BRAF^V600E-mutant mCRC in Japan.

Keywords: Colorectal cancer; KRAS Exon2; KRAS non-Exon2; NRAS.