While observational studies suggest favorable associations between statin use and prostate cancer (CaP) outcomes, data from randomized-controlled trials remain inconclusive. Our study explores the relationship between statin use and survival outcomes in the context of the phase III ARAMIS study, a trial of darolutamide in the treatment of nonmetastatic castration-resistant prostate cancer.
We reviewed all 1,509 patients in the ARAMIS trial. Statin use was identified at baseline. Statin users were matched 1:2 with nonusers using a propensity score matching model. The primary endpoint was metastasis-free survival (MFS). Kaplan-Meier curves were plotted for MFS comparing statin users and nonusers across ARAMIS trial arms. A multivariate Cox proportional hazards model was fitted using the propensity-matched cohort and incorporating statin use and all covariates.
Of the 1,509 patients in ARAMIS, 334 (22.1%) were statin users. We matched 297 statin users to 550 nonusers. Characteristics appeared well balanced. Among nonusers, 331 (60.3%) and 219 (39.7%) were in the ARAMIS darolutamide and placebo arms, respectively. Among statin users, 179 (60.3%) and 118 (39.7%) were in the ARAMIS darolutamide and placebo arms, respectively. Overall, we found no significant difference in MFS between statin users and nonusers (HR 1.05, 95% CI 0.80-1.38 P = .72). However, we found significant interaction between statin use and ARAMIS trial arm. Specifically, statin use had a stronger association with MFS in the placebo arm (P = 0.024). However, this is likely coincidental and due to the statin-placebo patients having higher nodal positivity than the nonusers-placebo patients (14.3% vs. 5.5%). Statin use was similarly not associated with the secondary outcomes of PSA progression-free survival (P = 0.42), time-to-pain progression (P = 0.85), or overall survival (P = 0.15).
In our secondary analysis of the ARAMIS trial, statin users had similar MFS and secondary outcomes compared to nonusers. These results suggest pursuing further statin synergies with amide-based androgen receptor axis target agents may not be fruitful.
Urologic oncology. 2024 Oct 29 [Epub ahead of print]
Julian Chavarriaga, Katherine Lajkosz, Nishant Sangole, Linda Z Penn, Najia Khurram, Robert J Hamilton
Division of Urology, Department of Surgical Oncology, University Health Network & University of Toronto, Toronto, Ontario, Canada; Division of Urology, Cancer treatment and Research Centre (CTIC) Luis Carlos Sarmiento Angulo Foundation, Bogota D.C., Colombia; Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address: ., Division of Urology, Department of Surgical Oncology, University Health Network & University of Toronto, Toronto, Ontario, Canada; Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Medical affairs Department, Bayer Inc. Mississauga, Ontario, Canada., Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.