What does this research mean for the field?

Different androgen receptor pathway inhibitors (ARPIs) combined with androgen deprivation therapy (ADT) exhibit distinct toxicity profiles in prostate cancer patients, with all increasing fracture and hypertension risk, but varying significantly in risks for specific adverse events such as cardiac disorders, falls, skin toxicity, and mental impairment. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to compare the toxicity profiles of different androgen receptor pathway inhibitors (ARPIs) combined with androgen deprivation therapy (ADT) in prostate cancer patients.

May 30, 2026

Comparison of the toxicity profile of different ADT + ARPI combinations in prostate cancer (PC) patients (pts): A systematic review and meta-analysis.

Key Points

This study aims to compare the toxicity profiles of different androgen receptor pathway inhibitors (ARPIs) combined with androgen deprivation therapy (ADT) in prostate cancer patients.
Conducted a systematic review of trials assessing ADT + ARPI vs ADT alone.
Analyzed adverse events through meta-analysis using odds ratios (OR).
Included 21 trials with a total of 18,453 patients.
All ARPIs increased fracture risk: abi OR 2.07, apa OR 2.38, daro OR 1.52, enza OR 1.88.
Addition of ARPIs increased risk of hypertension: abi OR 1.87, apa OR 1.27, daro OR 1.27, enza OR 2.43.
Enzalutamide caused more asthenia (OR 1.64), falls (OR 2.39), fatigue (OR 1.53), hypertension (OR 2.43), and weight loss (OR 1.38) compared to other ARPIs.

Abstract

e17020 Background: ARPI selection in PC pts is primarily guided by comorbidities and drug interactions. To date, there are few direct comparisons between ARPIs with regard to toxicity profiles. Methods: we conducted a systematic review of all trials assessing treatment with ADT+ARPI vs ADT alone for PC pts, using the PubMed/Medline and Cochrane library databases. We then performed a meta-analysis including all adverse events (AEs) of interest: asthenia, cardiac arrhythmia, cardiac disorders (CD), coronary artery disease (CAD), falls, fractures, fatigue, hot flushes (HF), hypertension (HTN), mental impairment (MI), psychiatric disorders, seizure, skin toxicity (ST), weight loss (WL), weight gain. The comparison between ADT+ARPI vs ADT in terms of AEs was assessed using odds ratio (OR) as meta-analytic outcome. Results: We identified 21 trials including 18,453 pts (10,422 ADT+ARPI; 8,031 ADT): 7 studies evaluated abiraterone (abi), 4 apalutamide (apa), 4 darolutamide (daro) and 6 enzalutamide (enza). All ARPIs increased fracture risk (abi: OR 2.07 95%CI 1.17-3.68; apa: OR 2.38 95%CI 1.82-3.11; daro: OR 1.52, 95%CI 1.12-2.07; enza: OR 1.88, 95%CI 1.28-2.75) and HTN (abi: OR 1.87, 95%CI 1.43-2.45; apa: OR 1.27, 95%CI 1.09-1.47; daro: OR 1.27, 95%CI 1.02-1.58; enza: OR 2.43, 95%CI 1.5-3.95), vs ADT. The addition of abi increased the risk of CD (OR 1.43, 95%CI 1.18-1.73) and HF (OR 1.09, 95%CI 1.03-1.15), while no significant difference was found in other AEs. The addition of apa increased the risk of falls (OR 1.35, 95%CI 1.06-1.72), ST (OR 4.15, 95%CI 3.18-5.4) and WL (OR 3.08, 95%CI 2.08-4.57) no significant difference was found in other AEs. The addition of daro increased the risk of CAD (OR 1.57, 95%CI 1.03-2.4), while no significant difference was found in other AEs. The addition of enza increased the risk of asthenia (OR 1.64, 95%CI 1.35-1.99), falls (OR 2.39, 95%CI 1.77-3.24), fatigue (OR 1.53, 95%CI 1.25-1.86), HF (OR 1.64, 95%CI 1.26-2.14), MI (OR 2.77, 95%CI 2.02-3.79) and WL (OR 1.38, 95%CI 1.07-1.78) while no significant difference was found in other AEs. Analyzing the confidence intervals, enza caused more asthenia and HF than abi, more falls than daro and apa, and more HTN than apa while apa caused more ST and WL than daro and enza. Conclusions: Our results identified differences in toxicity profile of different ARPIs, which could help clinicians identify the most appropriate ARPI for each individual patient.

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