Mortality and Hospitalization Risk Following Oral Androgen Signaling Inhibitors Among Men with Advanced Prostate Cancer by Pre-existing Cardiovascular Comorbidities

Abstract

Background: Elderly patients (≥65 yr) with advanced prostate cancer and cardiovascular disease (CVD) conditions are often excluded from clinical trials of abiraterone acetate (AA) or enzalutamide (ENZ). Consequently, little is known about the effects of these medications on these vulnerable patients.Objective: To assess the short-term outcomes of AA and ENZ in patients with pre-existing CVDs. Design, setting, and participants:A population-based retrospective study. The Surveillance, Epidemiology, and End Results-Medicare-linked database was used to identify prostate cancer patients using AA or ENZ. Outcome measurements and statistical analysis:The primary endpoint was 6-mo allcause mortality, analyzed using modified Poisson regression modeling of relative risk (RR) adjusted for confounders and comorbidities.Results and limitations: Among eligible patients (2845 with AA and 1031 with ENZ), 67% had at least one pre-existing CVD. Compared with those without pre-existing CVDs, having one to two pre-existing CVDs was associated with 16% higher 6-mo mortality (RR = 1.16, 95% confidence interval [CI]: 1.00-1.36), and the risk increased further among those having three or more CVDs (RR = 1.56, 95% CI: 1.29-1.88). Most of the differences in survival of patients with pre-existing CVD condition occurred within the first 6 mo of treatment. Conclusions:After treatment with AA or ENZ, elderly prostate cancer patients with preexisting CVDs experienced higher short-term mortality than otherwise similar patients without CVDs. Mortality associated with CVDs did not depend on having received AA versus ENZ.Patient summary: Patients with pre-existing cardiovascular diseases (CVDs) experienced higher short-term mortality after abiraterone acetate or enzalutamide than those without preexisting CVDs. It is recommended that a multidisciplinary team, including a cardiologist, evaluate patients having pre-existing CVDs in the process of making treatment decisions and monitoring potential side effects.

Deep androgen receptor suppression in prostate cancer exploits sexually dimorphic renal expression for systemic glucocorticoid exposure

“…These effects may contribute to the recognized association between enzalutamide treatment and higher short-term Annals of Oncology mortality in men with pre-existing cardiovascular disease. 25 Asthenia and other hard-to-define central nervous system (CNS) effects, including mental status changes and mental impairment, are also noted to occur with potent AR antagonists. 26 One hypothesis is that some of these effects may be attributable to a GABAergic action in the CNS.…”

Cardiovascular Complications of Prostate Cancer Treatment

“…Therefore, there has been a growing concern about their safety in real-world populations, especially in the elderly or those with CV diseases. A population-based retrospective study from The Surveillance, Epidemiology, and End Results (SEER) database of patients using abiraterone or enzalutamide (n = 3,876) revealed that men with coexisting CV comorbidities have a higher mortality threat compared to individuals without a history of CV disorders ( Lu-Yao et al, 2020 ). However, there is also evidence that appropriate control of CV comorbidities before the treatment initiation may substantially reduce the CV risk of the prescribed therapy ( Verzoni et al, 2016 ).…”

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

“…The AR signaling has been a target of immense attention because of its involvement in PC. Indeed, the AR signaling pathway's molecular level defects can trigger PC growth, differentiation, metastasis, invasion, and aggressiveness [107]. New insights given to miRNAs and their interactions with different signaling cascades have become more and more significant, as they are chief modulators of almost all cells' machinery [108].…”