Association of RAS mutations with early progression after first-line systemic therapy in patients with initially unresectable colorectal cancer liver metastasis

Abstract Purpose Patients with initially unresectable colorectal cancer with liver metastases (IU-CRLM) need to undergo first-line systemic therapy with the aid of chemotherapy. However, the driver gene attributed to early progression in IU-CRLM patients after first-line systemic therapy remains unclear. Our study explored the RAS mutation status related to early progression in IU-CRLM patients. Methods A total of 193 IU-CRLM patients with RAS status detection were retrospectively enrolled from December 2012 to January 2020. We defined early progression as tumour progression within 6 months after first-line systemic therapy. Univariate and multivariate logistic regression for early progression were implemented to identify the risk factors. Results RAS mutations were found in 51 (26.0%) IU-CRLM patients. A total of 107 (55.4%) patients were confirmed to have early progression after first-line systemic therapy. RAS mutation was significantly related to early disease progression (66.7% vs. 49.3%, P=0.033). Logistic analysis results showed that RAS mutation (OR=2.962, 95% CI 1.354-6.478, P=0.007) was an independent risk factor for early disease progression. Conclusions Mutated RAS was an important risk factor for early progression in IU-CRLM patients after first-line systemic therapy.