The Impact of Renin-Angiotensin System Inhibitors Combined with Panitumumab on Survival in RAS Wild-Type Metastatic Colorectal Cancer

A growing body of evidence suggests potential impact of renin-angiotensin system inhibitors on tumor biology and treatment response in colorectal cancer. However, it still remains to prove their impact on survival when used in combination with panitumumab in patients with RAS wild-type (KRAS/NRAS wild-type) metastatic colorectal cancer. This study aimed to assess the impact of ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on progression-free survival (PFS) and overall survival (OS) in patients receiving panitumumab. This retrospective cohort study included 122 patients with histopathologically proven RAS wild-type metastatic colorectal cancer attending our clinics between January 2019 and April 2025. All patients had received first-line systemic chemotherapy. Patients were divided into two groups based on whether or not they received ACEI/ARB (users: n=52; non-users: n=70). PFS was defined as the time from the start of treatment until disease progression or death and OS was defined as the time from the start of treatment until death. The Kaplan–Meier method was used for survival analysis and prognostic factors were analyzed using univariate and multivariate Cox regression models. The median follow-up time was 58.9 (95% CI: 52.7–65.2) months. The median PFS was 16.32 (95% CI: 13.3–19.3) months in ACEI/ARB users and 10.97 (95% CI: 8.74–13.2) months in ACEI/ARB non-users (p=0.04). The median OS was 61.73 (95% CI: 54.5–68.9) months and 38.37 (95% CI: 28.7–47.9) months, respectively (p=0.018). The multivariate analysis demonstrated a significant association between ACEI/ARB usage and overall survival (HR: 0.47; 95% CI: 0.27–0.81; p=0.008). A subgroup analysis did not show a statistically significant difference between ACEIs and ARBs. ACEI/ARB usage was found to be associated with longer progression-free survival and overall survival in patients with RAS wild-type metastatic colorectal cancer. These data indicated that renin-angiotensin system inhibitors might play a potential role in tumor biology and treatment response. Prospective studies are needed to confirm these data in order to introduce them into clinical practice.