Mortality in Castration Resistant Prostate Cancer Patients With and Without Pre-Existing Cardiovascular Disease Receiving Oral Androgen Receptor Pathway Inhibitors.

Abstract

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. 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. 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). 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. Prostate cancer that no longer responds to hormone therapy is called castration‐resistant prostate cancer (CRPC). Two commonly used treatments for CRPC are oral androgen receptor pathway inhibitors (ARPis), which are pills, and chemotherapy, which is given by infusion. Many older men with CRPC also have cardiovascular disease (CVD) (such as heart disease or prior stroke), but these patients are often underrepresented in clinical trials. In this study, we used national Medicare data linked with cancer registry records to examine survival outcomes among 1438 older men with CRPC who received either ARPis or chemotherapy between 2012 and 2014. About half of the patients had pre‐existing CVD. After accounting for differences in patient characteristics between treatment groups, men who received ARPis had lower overall mortality and lower prostate cancer–specific mortality compared with those who received chemotherapy. These patterns were similar among patients with and without CVD. Because this was an observational study using administrative data, unmeasured differences between groups may still have influenced the results. Nonetheless, the findings provide real‐world evidence to help inform treatment decisions for older men with advanced prostate cancer.