Association of statin use with overall survival and cardiac adverse events in patients with advanced prostate cancer treated with apalutamide: A pooled analysis of TITAN and SPARTAN.

Abstract

137 Background: The impact of statins on overall survival (OS) in patients (pts) with advanced prostate cancer is not fully understood. We performed a pooled analysis of the TITAN and SPARTAN trials to determine if exposure to statins had an independent effect on OS and grade ≥3 cardiac adverse events (AE) in pts treated with androgen deprivation therapy (ADT) with/without apalutamide (APA). Methods: TITAN and SPARTAN randomized pts to receive ADT with/without APA either in metastatic hormone-sensitive or in non-metastatic castration-resistant prostate cancer, respectively. Pts had at least some duration of statin exposure during the assigned treatment which could have started before and ended during or after the assigned treatment. A stratified (for the trial) multivariable Cox proportional hazard model was applied to determine the association of statin use with OS. Adjusted (adj) OS was estimated for pts in each trial, separately. A multivariable stratified logistic regression model was applied to determine the association of statin exposure with grade ≥3 cardiac AE. Results: Out of 2190 pts included in this study, 1288 received APA (TITAN 517; SPARTAN 771) and 484 were exposed to statins. Statin exposure was associated with significantly superior OS among all APA-treated pts (adjusted hazard ratio [HR]: 0.58; 95% CI: 0.45-0.75) while the OS benefit was not significant among ADT-treated pts (adjusted HR: 0.83 [0.62-1.11]). Adjusted 3-year OS in pts with and without statins were 82% and 67% (adjusted difference: 15%; 95% CI: 6-24) in the APA arm of TITAN and 86% and 78% (adjusted difference: 8% [3-13]) in the APA arm of SPARTAN. Adjusted 3-year OS among pts with and without statins was 71% and 58% (adjusted difference: 13% [3-24]) in the ADT arm of TITAN and 77% and 75% (adjusted difference: -2% [-10 to 6]) in the ADT arm of SPARTAN. Statin exposure was associated with a higher risk of grade ≥3 cardiac AE in pts treated with APA (adjusted odds ratio [OR]: 2.92 [1.56-5.47]) and ADT (adjusted OR: 3.06 [1.18-7.89]). Conclusions: In this exploratory analysis, exposure to statins was associated with significantly improved OS in all APA-treated patients but not in ADT-treated patients. Statin exposure was also associated with a higher risk of grade ≥3 cardiac AE in all pts (APA and ADT), which could be attributed to pre-existing cardiac comorbidities requiring these patients to start statin.