Population-based Analysis of Treatment Toxicity Among Men With Castration-resistant Prostate Cancer: A Phase IV Study

Objective: To assess the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments at a population level, among all patients in Ontario particularly treated with newer agents, including abiraterone, enzalutamide, docetaxel, and cabazitaxel. Methods: We performed a population-based, retrospective cohort study of 2439 men aged ≥65 years treated for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003 to 2015 in Ontario, Canada. Our primary outcome was treatment-related toxicity, defined as hospitalizations and emergency room (ER) visits during mCRPC treatment. Based on toxicity profiles identified during phase III trials, we further identified specific treatment-related toxicity. We calculated hazard ratios (HRs) using multivariable Cox proportional hazards models with time-varying exposures. Results: Abiraterone and enzalutamide exposure were not associated with any-cause (P =.19 and.52, respectively) or treatment-related (P =.45 and.64, respectively) toxicities. In contrast, docetaxel exposure was associated with an increased risk of any-cause (HR 1.29, 95% confidence interval [CI] 1.15-1.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicities. Cabazitaxel exposure was associated with a significant risk of treatment-related toxicity (HR 5.94, 95% CI 1.87-18.92) but not any-cause toxicity (HR 2.37, 95% CI 0.59-9.63). Conclusion: Among patients with mCRPC, we failed to show any increased risk of hospitalizations and ER visits for treatment-related complications for abiraterone or enzalutamide. In contrast, treatment with intravenous chemotherapeutic agents was associated with an increased risk of hospitalizations and ER visits to manage these complications.