95P - Prognosis of Japanese patients with detailed RAS/BRAF mutant colorectal cancer

Background

RAS mutations are the most prominent oncogenic driver mutations in cancers, including colorectal cancer. Patients with metastatic colorectal cancer (mCRC) with mutant RAS are ineligible for anti-epidermal growth factor receptor (EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. In particular, mutations in the amino acid at position 12 in the KRAS protein are common, and the KRAS p.G12C mutation occurs in ∼3% of CRC cases and is often associated with poor prognosis. Nevertheless, no agent directly targeting mutant RAS has been clinically approved. The CodeBreak 100 trial revealed that a novel KRASG12C inhibitor, AMG510, has an attractive anti-tumor effect against KRASG12C-mutant solid tumors, including mCRC. However, there are no data about the clinical and prognostic features in Japanese patients with detailed RAS/BRAF V600E-mutant mCRC including KRASG12C. The aim of this multicenter retrospective study was to investigate the clinical and prognostic features in Japanese patients with detailed RAS/BRAF V600E-mutant mCRC.

Methods

Between August 2018 and July 2019, chemotherapy-naïve patients with mCRC from whom samples were collected and investigated for all RAS/BRAFV600E statuses were included in this study. The RAS/BRAFV600E status was determined using the MEBGEN RASKET-B kit, PCR-rSSO method.

Results

In total, 152 patients with mCRC (median age, 71 years; male, 71%; left-sided primary, 67.1%) were enrolled from three tertiary cancer centers. Of the patients, RAS/BRAF mutations were detected in 54.6% (KRAS codon 12, 27.0%; KRAS codon 13, 11.8%; minor RAS, 9.2%; BRAFV600E, 6.6%). BRAFV600E-mutant tumors were predominantly located on the right side (77.8%, p=0.005), and minor RAS-mutant tumors were located predominantly on the left side (92.9%, p=0.037). Minor RAS-mutant tumors were associated with significantly shorter survival times than those associated with RAS wild-type {hazard ratio (HR)=2.65 [95% confidence interval (CI), 0.99 to 7.07], p=0.043} and major RAS-mutant tumors (HR=5.15 [95% CI, 1.56 to 16.98], p=0.003).

Conclusions

This multicenter study revealed the clinical and prognostic features in Japanese patients with detailed RAS/BRAFV600E-mutant mCRC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Hironaga Satake.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.