NEW findings revealed that a combination of androgen receptor signalling inhibitors (ARSIs) with androgen deprivation therapy (ADT) was associated with an elevated risk of cardiovascular events in locally advanced and metastatic prostate cancer (PCa). ADT is the standard first-line treatment for symptomatic metastatic PCa. The introduction of ARSIs in combination with ADTs has dramatically transformed the treatment landscape, improving survival outcomes in metastatic PCa patients. ADT is an established cardiovascular event risk factor, and combination therapy leads to an increased period of intense androgen deprivation. However, the cardiovascular effect of ARSIs is not delineated. Therefore, researchers conducted a systematic review and meta-analysis to assess the incidence of CV events with the addition of ARSI to ADT.
The systematic review utilized PRISMA guidance, and studies were searched for on PubMed, Scopus, Web of Science, EMBASE, and ClinicalTrials.gov databases up to May 2023. Eligible studies included randomized clinical trials of ARSI agents added to standard-of-care ADT that recorded cardiovascular events in patients with hormone-sensitive prostate cancer (HSPC), and locally advanced, metastatic, and castration-resistant prostate cancer (CRPC). Independent screening and evaluation of eligible studies for inclusion were performed by two authors. A random-effect meta-analysis was conducted of 24 randomized clinical trials, comprising 22,166 patients with locally advanced or metastatic disease, to estimate risk ratios for the incidence of cardiovascular events.
Results found that ARSI therapy was associated with a 75% increased risk of all grades of cardiovascular events (risk ratio [RR] 1.75, 95% confidence ratio [CI] 1.50-2.04, p<0.001). Moreover, the addition of ARSI therapy was linked to a more than twofold increase in the risk of ≥ grade 3 (RR 2.10, 95% 1.72-2.55, p<0.001) cardiovascular event and CV-related death (RR 2.02, 95% CI 1.32-3.10, p=0.001). Specifically, ARSI therapy was associated with 2.25 RR for hypertension (95% CI 1.74-2.90) along with increased risk for all grade 3 or higher cardiovascular events excluding venous thromboembolism.
This systematic review and meta-analysis led researchers to conclude that ARSI is associated with an increased risk of cardiovascular events across the PCa disease spectrum. Furthermore, patients with PCa should receive counselling regarding the potential of increased cardiovascular mevent risk with ARSI and surveillance for such events. Finally, the authors stated that their findings are a call to action for the medical community to reexamine CV risk estimation models that exclude cancer and respective therapeutics as risk modifiers.
Reference:
El-Taji O et al. Cardiovascular events and androgen receptor signaling inhibitors in advanced prostate cancer: a systematic review and meta-analysis. JAMA oncology. 2024;DOI:10.1001/ jamaoncol.2024.1549
