Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer

Abstract

Background Abiraterone and enzalutamide are the most common oral agents for the treatment of men with advanced prostate cancer. To understand their safety profiles in real-world settings, we examined the association between the use of abiraterone or enzalutamide and the risk of metabolic or cardiovascular adverse events while on treatment. Methods Men with advanced prostate cancer and their use of abiraterone or enzalutamide were identified in a 20% sample of the 2010-2017 national Medicare claims. The primary composite outcome was the occurrence of a major metabolic or cardiovascular adverse event, defined as an emergency room visit or hospitalization associated with a primary diagnosis of diabetes, hypertension, or cardiovascular disease. The secondary composite outcome was the occurrence of a minor metabolic or cardiovascular adverse event, defined as an outpatient visit associated with a primary diagnosis of the aforementioned conditions. Risks were assessed separately for abiraterone and enzalutamide using Cox regression. All statistical tests were 2-sided. Results Compared to men not receiving abiraterone, men receiving abiraterone were at increased risk of both a major composite adverse event (HR 1.77, 95% CI 1.53-2.05, P<0.001) and a minor composite adverse event (HR 1.24, 95% CI 1.05-1.47, P=0.01). Compared to men not receiving enzalutamide, men receiving enzalutamide were at an increased risk of a major composite adverse event (HR 1.22, 95% CI 1.01-1.48, P=0.04) but not a minor composite adverse event (HR 1.04, 95% CI 0.83-1.30, P=0.75). Conclusion Careful monitoring and management of men on abiraterone or enzalutamide through team-based approaches are critical.

Real‑world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration‐resistant prostate cancer

“…A recent study regarding adverse events with ARSIs for PC patients in high-volume real-world settings reported that men given AA plus prednisone (n = 2736) had a heightened likelihood of requiring emergency care or hospital admission in connection with diabetes, hypertension, or cardiovascular ailments compared to AA-naive men (HR 1.77, 95% CI 1.53-2.05, p < 0.001). 24 On the contrary, men who received Enz (n = 2466) were at relatively modest increased risk of those events compared to men who did not receive Enz (HR 1.22, 95% CI 1.01-1.48, p = 0.040). Given that the characteristics of patients treated with Enz and AA are nearly identical, the substantially different magnitude of risk suggests that treatment with AA plus prednisone may potentially lead to metabolic and cardiovascular undesirable occurrences.…”

“…For men with advanced PC, who already face a heightened risk of metabolic and cardiovascular incidents due to their older age and simultaneous utilization of chronic androgen deprivation, 22,23 adverse events stemming from AA plus prednisone or Enz therapy may significantly influence their overall well‐being and life quality. A recent study regarding adverse events with ARSIs for PC patients in high‐volume real‐world settings reported that men given AA plus prednisone ( n = 2736) had a heightened likelihood of requiring emergency care or hospital admission in connection with diabetes, hypertension, or cardiovascular ailments compared to AA‐naive men (HR 1.77, 95% CI 1.53–2.05, p < 0.001) 24 . On the contrary, men who received Enz ( n = 2466) were at relatively modest increased risk of those events compared to men who did not receive Enz (HR 1.22, 95% CI 1.01–1.48, p = 0.040).…”

Second generation androgen receptor antagonists and challenges in prostate cancer treatment

“…A retrospective observational study has reported falls as a CNS-related event in patients with metastatic prostate cancer receiving enzalutamide (4.6%) [31]. Additionally, the clinical application of secondgeneration AR antagonists may increase the risk of cardiovascular events [56,57]. A recent meta-analysis involving 4110 nmCRPC patients treated with enzalutamide, darolutamide, or apalutamide has indicated that the application of second-generation AR antagonists is associated with significantly increased risk of cardiovascular events including stroke, heart failure, and peripheral vascular disease [42].…”

Mental health care utilization among men with castration‐resistant prostate cancer receiving abiraterone or enzalutamide

“…Given their similar efficacy, patients and providers weigh the unique toxicity profiles of each drug, among other factors (e.g., cost), when choosing between the two. Abiraterone has a higher incidence of liver and cardiac toxicity and requires concurrent prednisone use whereas enzalutamide is associated with fatigue and falls and is contraindicated in those with a seizure disorder 10–12 …”

“…Abiraterone has a higher incidence of liver and cardiac toxicity and requires concurrent prednisone use whereas enzalutamide is associated with fatigue and falls and is contraindicated in those with a seizure disorder. [10][11][12] To add to the distinctions between these two antiandrogens, post-marketing data have conflicting findings as to whether abiraterone or enzalutamide is associated with an impact on emotional functioning. [13][14][15][16] Emotional functioning is of particular relevance to men with CRPC as the backbone treatment for the disease, androgen deprivation therapy (ADT), is associated with an increased risk of depression and anxiety.…”