Pharmacoepidemiol Drug Saf. 2026 Jul;35(7):e70405. doi: 10.1002/pds.70405.
ABSTRACT
BACKGROUND: Men with castration-resistant prostate cancer (CRPC) who have a pre-existing history of cardiovascular disease (CVD) or other comorbidities are often excluded from clinical trials involving oral androgen receptor pathway inhibitors (ARPi). In this study, we compared all-cause and prostate cancer-specific mortality among CRPC patients, with and without a pre-existing history of CVD, receiving ARPi compared to chemotherapy.
METHODS: Men with CRPC were identified using the Surveillance, Epidemiology, and End Results-Medicare Linked Database from 2004 to 2015. Patients were grouped into two analytical cohorts by drug use. Inverse probability treatment weights (IPTW)-adjusted Cox models and Fine-Gray subdistribution hazards models were used to evaluate associations between ARPi and chemotherapy, and between ENZ and AA for all-cause mortality and cancer-specific mortality separately.
RESULTS: The study cohort included 1438 men with CRPC. Nearly 54.4% of patients had a pre-existing history of CVD. Patients with a pre-existing history of CVD had a higher incidence of all-cause and prostate cancer-specific mortality compared to patients without a history of CVD (all-cause mortality: 69.7% vs. 59.3%, prostate cancer-specific mortality: 56.0% vs. 49.5%, respectively). In the pre-existing history of CVD cohort, the IPTW-adjusted Cox model showed a significantly lower all-cause mortality in patients who received APRi, enzalutamide, and abiraterone, versus chemotherapy (IPTW-adjusted hazard ratio [AHR], 0.56; 95% Confidence Interval [CI], 0.48-0.64; p-value < 0.001). Further, the IPTW-adjusted competing risk model showed significantly lower prostate cancer-specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW-AHR, 0.48; 95% CI, 0.41 to 0.57; p-value < 0.001). In the without pre-existing history of CVD cohort, the adjusted Cox model showed significantly lower all-cause mortality in patients who received APRi than those who received chemotherapy (IPTW-AHR, 0.49; 95% CI, 0.41-0.60; p-value < 0.001). Whereas the IPTW-adjusted competing risk model showed significantly lower prostate cancer-specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW-AHR, 0.52; 95% CI, 0.42-0.64; p-value < 0.001).
CONCLUSION: In this population-based cohort of older men with castration-resistant prostate cancer, treatment with oral androgen receptor pathway inhibitors was associated with lower estimated risks of all-cause and prostate cancer-specific mortality compared with chemotherapy in patients with and without pre-existing CVD. These findings add real-world comparative effectiveness evidence for patient populations not well represented in randomized clinical trials; however, given the observational design and limitations of administrative data, residual confounding and unmeasured clinical differences may have influenced the results.
PMID:42322109 | DOI:10.1002/pds.70405