The impact of abiraterone and enzalutamide on hypokalemia incidence in patients with prostate cancer: a systematic review and meta-analysis

To systematically evaluate the incidence of hypokalemia associated with novel androgen receptor axis-targeted therapies (ARATs)—specifically abiraterone, enzalutamide, and their combination—in patients with advanced prostate cancer. A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted to identify published randomized controlled trials (RCTs). Risk of bias was assessed using the Cochrane Risk of Bias tool. A random-effects model was employed to pool risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity was quantified using the I 2 statistic, and subgroup analyses were stratified by the specific ARAT regimen. Publication bias was evaluated utilizing funnel plots. Eight unique RCTs (comprising 9 published reports) involving 9,298 patients were included. The overall pooled analysis demonstrated a significantly increased risk of all-grade hypokalemia in patients receiving ARATs compared to controls (RR = 3.11, 95% CI: 1.88–5.15, P < 0.001; I 2 = 91.9%). Subgroup analyses revealed that this risk was significantly elevated with abiraterone (RR = 3.25, 95% CI: 1.75–6.02, I 2 = 88.3%) and the combination of abiraterone plus enzalutamide (RR = 4.62, 95% CI: 2.65–8.03, I 2 = 48.6%), but not with enzalutamide (RR = 1.16, 95% CI: 0.96–1.39). Similarly, the risk of severe (grade ≥ 3) hypokalemia was significantly higher with ARAT treatment (RR = 4.54, 95% CI: 2.42–8.51, I 2 = 48.4%); the risk signal was strongest in combination regimens (RR = 9.34, 95% CI: 1.71–50.90), although this estimate was based on limited data. Based on our preliminary findings, ARAT therapies, particularly abiraterone and combination regimens, are significantly related to the increased risk of hypokalemia in patients with advanced prostate cancer. Vigilant monitoring and the proactive management of serum potassium levels are strongly warranted in clinical practice.