Risk of therapy-related adverse events in men on abiraterone or enzalutamide, a IPD meta-analysis of clinical trial data

Background: Prostate cancer (PCa) is the most common cancer and second leading cause of death among men; over 260,000 men are diagnosed yearly and nearly 35,000 will die from the disease. Patients receive first generation androgen deprivation therapy. First-generation androgen deprivation therapy (ADT) blocks the secretion of testosterone and other androgens and is first-line therapy. PCa requires testosterone (an androgen) in order to grow, by depriving the body of the androgen testosterone (the male sex hormone) ADT may slow the cancer’s growth and temporarily shrink the cancer. However, PCa patients are at increased risk of therapy-related adverse events (AEs), including cardiovascular disease (CVD) outcomes. The introduction of newer agents called androgen receptor targeted (ART) drugs to ADT may further increase therapy-related AE and CVD risk. ARTs work in two ways, either by blocking the site (androgen receptor) on the tumor so it cannot receive androgens (enzalutamide) depriving the tumor of androgens or by blocking androgen synthesis (abiraterone); both means decrease a tumor’s ability to grow. There is no clear recommendation in clinical guidelines to recommend one drug over the other, and the choice of treatment options complicates clinical decision-making. This trial will conduct a comparative analysis using established statistical methods and develop guidance from this analysis to aid clinician decision-making and thereby enhancing patient care. Is there a difference in outcomes according to patient type based on drug received? Alternatively, are the outcomes similar for all patients regardless of drug choice?