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Abstract
Oral androgen signaling inhibitors (OASI), Enzalutamide (ENZ) and Abiraterone Acetate (AA) are both first-line treatments for metastatic castration-resistant prostate cancer (mCRPC), but the comparative effectiveness of these treatments has not been fully elucidated. Notably, men with mCRPC who received OASI were excluded from clinical trials if they had a pre-existing cardiovascular disease (CVD) and other comorbidities. Such practice limits the external validity of these trials, and findings may not be generalizable to patients with pre-existing comorbidities. This study sought to examine all-cause and prostate cancer-specific mortality, the incidence of new thromboembolic events (TE), and whether ENZ compared to AA is associated with a longer time to starting oral opioids and chemotherapy in mCRPC patients.An active comparator new-user design was used to identify 3,237 men diagnosed with likely CRPC using the Surveillance, Epidemiology, and End Results-Medicare Linked Database from 2011 to 2016. Patients were stratified by CVD history. Within each CVD stratum (pre-existing CVD versus no pre-existing CVD), patients were further divided into OASI versus chemotherapy new-user groups. Furthermore, we compared AA versus chemotherapy, and ENZ versus chemotherapy in the subgroup analyses within each analytical cohort. To assess the difference between AA and ENZ in men with and without CVD history. Inverse probability treatment weights (IPTW)-adjusted time-varying Cox models were used to evaluate associations between OASI and all-cause mortality and time-to-first use of oral opioids and chemotherapy. Inverse probability treatment weights (IPTW)-adjusted Fine‐Gray competing risk models were used to evaluate the potential association of OASI and prostate cancer-specific mortality, TE events, and switching drugs from ENZ to AA or AA to ENZ. Multiple sensitivity analyses were conducted.
A total of 2,147 patients had pre-existing CVD, of which 1,498 (70%) received OASI. Findings from this study suggested that OASI, both ENZ and AA, appeared comparatively with better effectiveness profile than chemotherapy. OASI was associated with preferable all-cause mortality, prostate specific-cause mortality, and lower TE events than chemotherapy for all groups, including those with pre-existing CVD. In fact, those with pre-existing CVD showed numerically better relative risk in response to OASI. ENZ and AA both showed beneficial effects compared to chemotherapy, with ENZ showing numerically greater benefits across groups, particularly among those with pre-existing CVD. When comparing ENZ vs. AA, patients who received ENZ showed a significant delay in using oral opioids and chemotherapy compared with other patients who received AA.