6A-03 - Incident type II diabetes amongst older men with metastatic castration-resistant prostate cancer treated with abiraterone versus enzalutamide

Background: Abiraterone and enzalutamide are androgen receptor pathway inhibitors (ARPIs) used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone is co-administered with steroids such as prednisone which may increase diabetes risk; additionally, the regimens have different mechanisms of action. The comparative diabetogenic safety of abiraterone versus enzalutamide has not been evaluated in population-based studies.

Objectives: The objective was to determine if initiation and sustained use of abiraterone, compared to enzalutamide, is associated with the two-year risk of developing incident type II diabetes (T2DM) amongst a real-world population of older adult men with mCRPC.

Methods: We implemented an active comparator, new user cohort study design leveraging the Surveillance-Epidemiology and End Results (SEER)-Medicare linked database (claims 2004-2019). The study population focused on older adult men (≥ 67 at index date) diagnosed with mCRPC who initiated either abiraterone or enzalutamide as first-line ARPI treatment between 2012 – 2017, an era during which mCRPC was the only labeled indication for either drug. We estimated the comparative effects of sustained ARPI use on the two-year risk of developing incident T2DM, representing an "on-treatment" effect. T2DM was identified using a previously validated claims-based algorithm that had a 95.8% specificity. A marginal structural model with time-varying inverse probability of treatment weights (IPTW) was used to account for measured time-varying confounders. Broadly, confounders included demographics, tumor characteristics, past cancer treatments, comorbidities, and comedications that may increase the risk of diabetes. The two-year risk of T2DM was estimated using a weighted Aalen-Johansen estimator to account for death as a competing event.

Results: The study population consisted of 2,321 abiraterone and 1,369 enzalutamide initiators (total n= 3,690. The median age was 77 (range 67 – 98). 81.1% of men were non-Hispanic white, 90.1% were most recently taking gonadotropin-hormone releasing agonists at the time of ARPI initiation, and 33.4% had metastatic prostate cancer at initial diagnosis. The weighted analysis found that the two-year risk of diabetes diagnosis was higher in abiraterone (12.5%; 95% confidence interval (CI): 9.5%, 15.6%) compared to enzalutamide (7.0%; 95% CI: 4.3%, 9.8%), with a risk difference of 5.5 percentage points (95% CI: 1.3, 9.7).

Conclusions: Amongst older adult men with mCRPC, abiraterone, which is co-administered with steroids, may increase the risk of developing T2DM.