1820P - Cardiovascular effects of androgen receptor signalling inhibitors in the treatment of advanced and metastatic prostate cancer: A systematic review and meta-analysis of randomised controlled trials

Background

Cardiovascular (CV) events remain a significant cause of mortality amongst men with advanced and metastatic prostate cancer (PCa). The introduction of novel androgen receptor signalling inhibitors (ARSI) has transformed the treatment landscape of PCa in recent years, however their impact on CV toxicity remains unclear. We aimed to assess the CV effects of ARSI treatment in combination with standard of care (SOC) in advanced and metastatic PCa.

Methods

Systematic search of PubMed, SCOPUS, Web of Science, EMBASE and Clinicaltrials.gov were performed to identify randomized controlled trials (RCTs) comparing the addition of ARSI agents (Enzalutamide, Abiraterone, Apalutamide and Darolutamide) with SOC in treatment of non-metastatic and metastatic PCa, across both hormone-sensitive and castrate resistant settings. Outcomes of interest included: CV events defined by CV event grade (primary outcome), hypertension, acute coronary syndrome (ACS), cardiac dysrhythmia, CV death, cerebrovascular event, and venous thromboembolism (secondary outcomes).

Results

A total of 22 studies (n=22,967) were eligible for inclusion. ARSI therapy increased risk of any grade CV event (RR 1.72, 1.49-2.00, p<0.0001) and grade ≥ 3 CV events (RR 1.98 [1.58-2.48] p<0.0001). ARSI therapy also resulted in an increase in grade ≥ 3 hypertension (RR 2.02 [1.62-2.53] p<0.0001), ACS (RR 2.00 [1.46-2.74] p<0.0001), grade ≥3 cardiac dysrhythmia (RR 1.64 [1.23-2.19] p=0.0007), CV related death (RR 1.88 [1.22-2.89] p=0.004) and cerebrovascular events (RR 1.76[1.33-2.34] p<0.0001) across all PCa settings. Subgroup analysis demonstrated increased risk of all CV events and grade ≥3 across the disease spectrum (RR for all CV events: non-metastatic hormone sensitive PCa 2.20 [1.4-3.47], p<0.0007; metastatic hormone sensitive PCa 1.69 [1.39-2.06], p<0.0001; metastatic castrate resistant PCa 1.53 [1.36-1.71], p<0.0001).

Conclusions

There is compelling evidence indicating a significantly increased risk of all and high-grade CV events in men treated with ARSIs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Genitourinary Cancer Research Group, University of Manchester, Manchester, United Kingdom.

Funding

Has not received any funding.

Disclosure

N.W. Clarke: Non-Financial Interests, Institutional, Other, Investigator on PRONOUNCE Trial. All other authors have declared no conflicts of interest.