Worst outcomes according to RAS mutation variants: an analysis in patients with metastatic colorectal adenocarcinoma.

Purpose: Over 50% of metastatic colorectal cancers harbor RAS mutations. It is unclear if different mutation variants have an impact on survival. The purpose of this study was to evaluate the impact of these mutations on colorectal cancer survival.

Methods: The charts of all cases of metastatic colorectal cancer diagnosed between January 2005 and January 2016 in a tertiary hospital in Brazil were reviewed. Inclusion criteria were complete data on clinical staging, treatments received and all-RAS testing. Multivariate Cox proportional survival models were used to evaluate the impact of specific RAS variants on survival.

Results: There were 151 eligible patients and 61.6% had RAS alterations, the most common G12D (11.9%) and G12A (8.6%). Most patients received chemotherapy, including oxaliplatin (79%), irinotecan (53%) and bevacizumab (59%). Among RAS-wild type patients, 46% received anti-EGFR therapy. Median survival was 39.2 months for RAS-wildtype, 18.8 months for RAS G12A and 34.6 for other RASmutant patients (multivariate analysis for G12A vs RASwild type HR 1.94; 95% CI 0.83-5.51; p=0.12).

Conclusion: Patients with metastatic colorectal cancer who have RAS mutations have shorter overall survival. Regarding the impact of specific KRAS alterations, G12A mutations have a worse prognosis.