Clinical and prognostic characteristics of metastatic colorectal cancer with minor <i>RAS</i> mutations

Metastatic colorectal cancer (mCRC) presents notable therapeutic challenges. Rat sarcoma virus (<i>RAS</i>) mutations, including those in <i>KRAS</i> exon 2, are critical for treatment decisions; however, the role of minor <i>RAS</i> mutations (<i>KRAS</i> exons 3 and 4, and <i>NRAS</i>) remains underexplored. Because these mutations are increasingly identified in routine practice due to advances in <i>RAS</i> mutation testing that now routinely includes <i>KRAS</i> exons 3 and 4, and <i>NRAS</i>, clarifying their clinical relevance has become important for ensuring appropriate treatment selection. The present study aimed to compare the clinical and prognostic characteristics of patients with mCRC with minor <i>RAS</i> mutations to those with <i>KRAS</i> exon 2 mutations. To this end, data were retrospectively collected from patients with mCRC and <i>RAS</i> mutations between August 2018 and December 2023. Patients were grouped based on <i>RAS</i> mutation subtype: <i>KRAS</i> exon 2 or minor <i>RAS</i> mutations. <i>RAS</i> mutation testing was performed using the MEBGEN RASKET™-B kit. Clinical characteristics, tumor location, metastatic patterns and survival outcomes were analyzed. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazards regression models. Of 202 patients with <i>RAS</i> mutations, 170 had <i>KRAS</i> exon 2 mutations, whereas 32 exhibited minor <i>RAS</i> mutations (20 with non-exon 2 <i>KRAS</i> mutations and 12 with <i>NRAS</i> mutations). Minor <i>RAS</i> mutations were more common in left-sided CRC. No significant differences in background were observed between the two groups. Log-rank OS was comparable for patients with <i>KRAS</i> exon 2 and minor <i>RAS</i> mutations. OS and PFS with first-line bevacizumab-containing therapy were also similar between the two groups. In conclusion, the prognostic impact of minor <i>RAS</i> mutations appears to be comparable to that of <i>KRAS</i> exon 2 mutations, suggesting that the current treatment strategies for <i>RAS</i>-mutant CRC may not require modification based on these findings.