Prognostic Impact of RAS Mutation and Biologic Therapy in Second-Line Treatment of De-Novo Metastatic Colorectal Cancer: A Real-World Retrospective Analysis
Gözde Ağdaş1, Mehmet Salim Demir11Department of Medical Oncology, Van Training and Research Hospital, Van, Türkiye
Objectives: For patients with de novo metastatic disease who progress after first-line therapy, optimal second-line treatment selection remains challenging, particularly regarding the choice between anti-EGFR and anti-VEGF biologic agents and the impact of molecular markers such as RAS mutation status and metastatic site. Methods: This retrospective analysis included 62 patients with de novo mCRC who received second-line chemotherapy at a single center. Demographic, clinicopathological, and treatment data were collected. Overall survival (OS) and progression- free survival (PFS) were estimated using Kaplan–Meier methods. Univariate and multivariate Cox proportional hazards models were employed to identify independent predictors of survival. Subgroup analyses were performed to compare outcomes by biologic type and RAS status. Results: The cohort had a balanced sex distribution (50% male, 50% female), with a mean age of 57.7±10.4 years. Tumor localization was evenly distributed (left colon, 33.9%; right colon, 32.3%; rectum, 33.9%). RAS mutation status was nearly balanced (mutant, 48.4%; wild-type, 51.6%). At diagnosis, the most common metastatic site was liver-only (53.2%). Second-line biologic use was 74%. Median OS from second-line initiation was 19.2 months (95% CI: 15.8–22.6), with 1-year and 2-year survival rates of 68% and 42%, respectively. Median PFS was 7.8 months (95% CI: 6.5–9.1). RAS wild-type patients demonstrated significantly longer OS than mutant patients (21.8 vs. 16.4 months, p=0.04). Peritoneal metastases showed a trend toward worse outcomes (median OS, 14.2 months; p=0.09). In multivariate analysis, RAS mutation remained the only significant independent predictor of mortality (HR=1.74, 95% CI: 1.08–2.80; p=0.02). Comparison of biologic types revealed that anti-VEGF therapy was associated with a trend toward improved overall survival compared with no biologic therapy (HR=0.55, 95% CI: 0.30–1.01; p=0.05), with a nonsignificant trend favoring anti-VEGF over anti-EGFR therapy. Conclusion: This real-world analysis confirms the prognostic significance of RAS mutation in de novo mCRC patients receiving second-line therapy and suggests a potential survival benefit associated with biologic use, though this did not reach statistical significance in multivariate analysis. The findings align with recent large-scale registry data and network meta-analyses, supporting current treatment paradigms while highlighting the need for larger studies to refine biologic selection based on molecular and clinical subtypes. Keywords: Anti-EGFR, Anti-VEGF, Metastatic Colorectal Cancer, RAS Mutation, Second-Line Chemotherapy
Cite This Article
Ağdaş G, Demir M. Prognostic Impact of RAS Mutation and Biologic Therapy in Second-Line Treatment of De-Novo Metastatic Colorectal Cancer: A Real-World Retrospective Analysis. EJMI. 2026; 10(3): 385-391
Corresponding Author: Gözde Ağdaş