Impact of metformin on outcomes with immune checkpoint inhibitors in renal cell carcinoma: A large-scale retrospective analysis.

Abstract

e16558 Background: Immune checkpoint inhibitors (ICIs) are a mainstay in the treatment of renal cell carcinoma (RCC). Metformin, a commonly used biguanide for type 2 diabetes, has demonstrated anti-tumor and immunomodulatory effects that may enhance ICI efficacy. However, the clinical impact of concurrent metformin use on outcomes in patients with RCC treated with ICIs remains unclear. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, a database of electronic medical records from 158 healthcare organizations. We identified patients with RCC using ICD-10-CM C64 who were initiated on ICIs ( nivolumab, pembrolizumab and avelumab) and were divided into two cohorts: those receiving concurrent metformin and those who were not. Propensity score matching (PSM) was performed in 1:1 ratio to balance the cohorts for age, sex, race, comorbidities, and concomitant medications. The primary outcome was overall survival (OS) over a 3-year follow-up period. Secondary outcomes included Major Adverse Cardiovascular Events (MACE) and immune-related adverse events (irAEs) including pneumonitis, colitis, thyroiditis, and skin eruptions. Results: A total of 12,271 patients with RCC treated with ICIs were identified: 1,321 in the Metformin cohort and 10,950 in non-metformin cohort. After 1:1 PSM, two well-balanced cohorts of 1,132 patients each were analyzed. Baseline characteristics were statistically similar between both cohorts (p > 0.05; Table 1). Metformin use in combination with ICI was associated with a significantly higher survival probability compared with ICI alone (61.40% vs 51.79%; HR 0.75, 95% CI 0.65–0.87). There was no statistically significant difference in the incidence of serious immune-mediated toxicities, including pneumonitis, thyroiditis, skin eruptions, and colitis and MACE. Conclusions: In this large-scale, real-world analysis, concurrent metformin use was associated with significantly improved OS in patients with RCC treated with immune checkpoint inhibitors. These findings suggest that metformin may serve as a beneficial adjuvant to therapy. However, additional prospective clinical trials should be performed to validate these findings and further elucidate the potential driving signaling mechanisms. Baseline characteristics after PSM. Characteristic RCC with Metformin (N=1,132) RCC without Metformin (N=1,132) P value Age at index [mean +/- SD (years)] 64.6 +/- 9.8 64.5 +/- 11.1 0.829 Sex Female, n (%) 298 (26.3) 293 (25.9) 0.811 Male, n (%) 834 (73.7) 839 (74.1) 0.010 Race White, n (%) 841 (74.3) 842 (74.4) 0.962 Hispanic, n (%) 119 (10.5) 126 (11.1) 0.636 Black or African American, n (%) 69 (6.1) 59 (5.2) 0.363