Background Treatments for metastatic castration‐resistant prostate cancer (CRPC) differ in toxicity, administration, and evidence. In this study, clinical and nonclinical factors associated with the first‐line treatment for CRPC in a national delivery system were evaluated. Methods National electronic laboratory and clinical data from the Veterans Health Administration were used to identify patients with CRPC (ie, rising prostate‐specific antigen [PSA] on androgen deprivation) who received abiraterone, enzalutamide, docetaxel, or ketoconazole from 2010 through 2017. It was determined whether clinical (eg, PSA) and nonclinical factors (eg, race, facility) were associated with the first‐line treatment selection using multilevel, multinomial logistic regression. The average marginal effects (AMEs) were calculated of patient, disease, and facility characteristics on ketoconazole versus more appropriate CRPC therapy. Results There were 4998 patients identified with CRPC who received first‐line ketoconazole, docetaxel, abiraterone, or enzalutamide. After adjustment, increasing age was associated with receipt of abiraterone (adjusted odds ratio [aOR], 1.07; 95% credible interval [CrI], 1.06‐1.09) or enzalutamide (aOR, 1.10; 95% CrI, 1.08‐1.11) versus docetaxel. Greater preexisting comorbidity was associated with enzalutamide versus abiraterone (aOR, 1.53; 95% CrI, 1.23‐1.91). Patients with higher PSA values at the start of treatment were more likely to receive docetaxel than oral agents and less likely to receive ketoconazole than other oral agents. African American men were more likely to receive ketoconazole than abiraterone, enzalutamide, or docetaxel (AME, 2.8%; 95% CI, 0.7%‐4.9%). This effect was attenuated when adjusting for facility characteristics (AME, 1.9%; 95% CI, –0.4% to 4.1%). Conclusions Clinical factors had an expected effect on the first‐line treatment selection. Race may be associated with the receipt of a guideline‐discordant first‐line treatment.

Background Abiraterone and enzalutamide are the most common oral agents for the treatment of men with advanced prostate cancer. To understand their safety profiles in real-world settings, we examined the association between the use of abiraterone or enzalutamide and the risk of metabolic or cardiovascular adverse events while on treatment. Methods Men with advanced prostate cancer and their use of abiraterone or enzalutamide were identified in a 20% sample of the 2010-2017 national Medicare claims. The primary composite outcome was the occurrence of a major metabolic or cardiovascular adverse event, defined as an emergency room visit or hospitalization associated with a primary diagnosis of diabetes, hypertension, or cardiovascular disease. The secondary composite outcome was the occurrence of a minor metabolic or cardiovascular adverse event, defined as an outpatient visit associated with a primary diagnosis of the aforementioned conditions. Risks were assessed separately for abiraterone and enzalutamide using Cox regression. All statistical tests were 2-sided. Results Compared to men not receiving abiraterone, men receiving abiraterone were at increased risk of both a major composite adverse event (HR 1.77, 95% CI 1.53-2.05, P<0.001) and a minor composite adverse event (HR 1.24, 95% CI 1.05-1.47, P=0.01). Compared to men not receiving enzalutamide, men receiving enzalutamide were at an increased risk of a major composite adverse event (HR 1.22, 95% CI 1.01-1.48, P=0.04) but not a minor composite adverse event (HR 1.04, 95% CI 0.83-1.30, P=0.75). Conclusion Careful monitoring and management of men on abiraterone or enzalutamide through team-based approaches are critical.