Impact of concomitant medication use on treatment outcomes in patients with RCC treated with immune checkpoint inhibitors.
Authors: Ahmet Yildirim, Mengting Wei, Yuan Liu, Yujin Choi, Lauren Suh, Dylan J. Martini, Caitlin Hartman, Greta Russler McClintock, Tony Zibo Zhuang, Wayne B. Harris, Jordan Alana Ciuro, Jacob E Berchuck, Jacqueline T Brown, Bassel Nazha, Bradley Curtis Carthon, Omer Kucuk, Viraj A. Master, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2025)

603 Background: Multiple studies on various cancer types have investigated concomitant statin, aspirin, and metformin use with immune checkpoint inhibitors. While some found improved OS and PFS, others reported no significant effect. In RCC, a retrospective study linked statins with improved OS and PFS. We aimed to evaluate the impact of statin, aspirin, and metformin use on survival in RCC patients treated with ICIs. Methods: A retrospective analysis was conducted on adult patients with advanced RCC treated with ICIs at Emory Winship Cancer Institute between 2018 and 2024. Concomitant medication use was assessed via chart review during active ICI treatment. Clinical benefit (CB) is determined by stable disease, partial response, and complete response. The multivariate analysis model for statin was built by controlling the age, gender, race, smoking status, IMDC risk group, ECOG PS, clear cell histology, prior treatments, and liver metastases. Variables were subject to backward elimination at the significant level of p &lt; 0.2. Results: Data from 400 patients were analyzed, with a median follow-up of 43.0 months (95% CI: 36.6-51.4). Of 400 patients, 138 (34.5%) were treated with ICI monotherapy, 131 (32.8%) treated with dual ICI combination, and 114 (28.5%) were treated with ICI and TKI combinations. 85 (21.3%) of the patients were African American or Black, 284 (71%) of them were White, and 239 (59.8%) were treated with ICIs as first-line. Statin use was more common among patients without prior treatment, without liver metastasis, older individuals, and those with a BMI ≥24.9. In univariate analysis, statin use showed potential associations with longer OS (HR 0.82; 95% CI 0.62-1.07 p=0.144), longer PFS (HR 0.81; 95% CI 0.64-1.02 p=0.071), and a higher likelihood of receiving CB (OR 1.85; 95% CI 1.17-2.92 p=0.008). However, multivariate analysis did not confirm significant differences in survival or CB. Survival outcomes are summarized in the table. Conclusions: Our analysis found no significant impact of concomitant statin, aspirin, or metformin use on RCC patient outcomes treated with ICIs. Further advancements in our understanding of tumor biology and checkpoint inhibitors might explain how concomitant medication affects treatment outcomes. Our study is limited by its retrospective design, and future prospective trials are necessary to provide definitive evidence. Univariate analysis of survival outcomes and clinical benefit. Overall Survival Progression-free survival Clinical Benefit HR (95% CI) p-value HR (95% CI) p-value OR (95% CI) p-value Statin Y n=170 0.82 (0.62-1.07) 0.144 0.81 (0.64-1.02) 0.071 1.85 (1.17-2.92) 0.008 Statin N n=230 - - - - - - Aspirin Y n=138 0.93 (0.70-1.24) 0.623 0.84 (0.66-1.07) 0.159 1.49 (0.93-2.40) 0.100 Aspirin N n=262 - - - - - - Metformin Y n=49 1.04 (0.68-1.57) 0.860 0.80 (0.55-1.15) 0.231 1.37 (0.68-2.78) 0.379 Metformin N n=351 - - - - -