Lipid-Lowering Therapy Use and Survival Outcomes in Advanced Renal Cell Carcinoma Treated with Toripalimab Plus Axitinib or Sunitinib: A Post Hoc Analysis of the Phase III RENOTORCH Trial

Abstract Background : Immune checkpoint inhibitor (ICI)-based combinations are important first-line treatments for advanced renal cell carcinoma (RCC), but factors influencing long-term outcomes remain incompletely understood. Lipid-lowering therapies have been suggested to affect cancer-related immune and metabolic processes, but their clinical relevance in advanced RCC remains unclear. This study aimed to evaluate the association between lipid-lowering therapy use and clinical outcomes in patients with advanced RCC. Methods : This post hoc analysis was based on data from the phase III RENOTORCH trial, which compared toripalimab plus axitinib with sunitinib as first-line treatment for advanced RCC. Patients were categorized according to recorded oral lipid-lowering therapy use during follow-up. Associations between lipid-lowering therapy and progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were evaluated using Cox regression, logistic regression, and inverse probability of treatment weighting (IPTW)-adjusted analyses. Results : Among 421 randomized patients, 113 (26.8%) received lipid-lowering therapy. In the toripalimab plus axitinib group, lipid-lowering therapy use was associated with improved OS after multivariable adjustment (HR 0.42, 95% CI 0.23–0.77; P=0.005) and IPTW adjustment (HR 0.48, 95% CI 0.26–0.88; P=0.018). No significant association between lipid-lowering therapy and survival outcomes was observed in the sunitinib group. Lipid-lowering therapy was not significantly associated with ORR or DCR. Exploratory analyses showed no consistent survival difference between statin and non-statin users, and triglyceride-related associations differed between treatment groups. Conclusions : In this post hoc analysis of the RENOTORCH trial, lipid-lowering therapy use was associated with favorable survival outcomes, particularly OS, among patients receiving toripalimab plus axitinib. These findings provide hypothesis-generating evidence regarding the potential relationship between lipid metabolism and outcomes of immunotherapy-based combination treatment in advanced RCC. Trial registration: ClinicalTrials.gov identifier: NCT04394975; registered on May 20, 2020.