A NEW systematic review and meta-analysis has revealed that adding androgen receptor signalling inhibitors (ARSIs) to standard androgen deprivation therapy (ADT) for advanced prostate cancer significantly increases the risk of adverse cardiovascular (CV) events. The study, conducted by Ashwin Sachdeva, University of Manchester, UK, and colleagues has shed light on an important issue amongst primary care physicians.
The analysis encompassed 24 randomized trials involving 22,166 patients with locally advanced or metastatic prostate cancer. The findings indicated that ARSI therapy is associated with a 75% higher risk of any-grade cardiovascular events (risk ratio [RR] 1.75, 95% confidence interval [CI] 1.50-2.04, P<0.001). The risk of severe (Grade 3 or higher) cardiovascular events more than doubled (RR 2.10, 95% CI 1.72-2.55, P<0.001), and the risk of cardiovascular-related death also increased significantly (RR 2.02, 95% CI 1.32-3.10, P=0.001).
“Patients with prostate cancer should be advised about and monitored for the potential of increased risk of CV events with initiation of ARSI therapy alongside conventional hormonal therapy,” the researchers advised.
Experts in the field commented on the study, emphasising the need for heightened awareness among healthcare providers. They called for the medical community to reassess CV risk estimation models, noting that current models often omit active cancer and specific cancer therapies as significant risk factors.
The researchers advised that all patients with prostate cancer undergo baseline CV risk assessments, with annual follow-ups, and adhere to stringent risk mitigation strategies. These strategies include guideline-directed statin therapy, aggressive blood pressure control, and lifestyle modifications such as a heart-healthy diet and regular aerobic exercise.
The team highlighted the importance of understanding the CV risks associated with combination therapies, especially as these treatments become more prevalent in earlier disease stages. The analysis showed that ARSI therapy increased the risk of severe hypertension, acute coronary syndrome, cardiac dysrhythmia, and cerebrovascular events.
The study also found variability in CV event rates among different ARSI drugs, with the highest risk observed with abiraterone and enzalutamide (RR 2.92, 95% CI 2.59-3.30) and the lowest with darolutamide (RR 1.30, 95% CI 1.09-1.54).
Despite the robust findings, the researchers acknowledged several limitations, including substantial heterogeneity across trials and inconsistent prespecification of CV outcomes. These factors could potentially bias the measurement of CV events.
Overall, the study underscores the need for careful cardiovascular monitoring and risk mitigation in prostate cancer patients receiving ARSI therapy.
Victoria Antoniou, EMJ, London, UK
Reference
El-Taji O et al. cardiovascular events and androgen receptor signaling inhibitors in advanced prostate cancer: a systematic review and meta-analysis. JAMA Oncol. 2024;DOI: 10.1001/jamaoncol.2024.1549.
