Cardiovascular Toxicity Associated With Androgen Receptor Axis-Targeted Agents in Patients With Prostate Cancer: A Meta-analysis of Randomized Controlled Trials

Clin Genitourin Cancer. 2024 Jun;22(3):102066. doi: 10.1016/j.clgc.2024.102066. Epub 2024 Mar 8.

Abstract

Introduction: Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities.

Patients and methods: We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted.

Results: A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, P = .04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, P = .007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, P = .05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, P = .02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, P = .01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, P = .04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, P = .03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, P = .01), respectively.

Conclusion: The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.

Keywords: Androgen receptor axis-targeting agent.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Androgen Receptor Antagonists / administration & dosage
  • Androgen Receptor Antagonists / adverse effects
  • Androgen Receptor Antagonists / therapeutic use
  • Androstenes / administration & dosage
  • Androstenes / adverse effects
  • Androstenes / therapeutic use
  • Benzamides / adverse effects
  • Cardiovascular Diseases / chemically induced
  • Clinical Trials, Phase III as Topic
  • Humans
  • Male
  • Nitriles / adverse effects
  • Phenylthiohydantoin / administration & dosage
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms* / drug therapy
  • Randomized Controlled Trials as Topic*
  • Receptors, Androgen / metabolism
  • Thiohydantoins / administration & dosage
  • Thiohydantoins / adverse effects
  • Thiohydantoins / therapeutic use

Substances

  • Androgen Receptor Antagonists
  • Receptors, Androgen
  • Phenylthiohydantoin
  • enzalutamide
  • Benzamides
  • Nitriles
  • apalutamide
  • Thiohydantoins
  • abiraterone
  • Androstenes
  • AR protein, human