Journal Article

The efficacy and safety of darolutamide combination therapy in advanced prostate cancer: a systematic review and meta-analysis of randomized controlled trials

Yuan, Huisheng, Wang, Zilong, Li, Zhenghao, Song, Changze, Huang, Hongyin, Li, Di, Chu, Junhao, Han, Zhuoyi, Cao, Xi

2026

Overview

Darolutamide is the next-generation androgen receptor inhibitor approved for the treatment of advanced prostate cancer, including non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). However, the efficacy and safety of darolutamide are nonetheless worthy of further clinical studies. The objective of this meta-analysis was to evaluate the overall survival, metastasis-free survival and various specific adverse events of darolutamide combination therapy in patients with mHSPC or nmCRPC. This meta-analysis was performed on PubMed, EMBASE, Web of Science, ClinicalTrials.gov, and the Cochrane Library for English-language articles to collect randomized clinical trials of darolutamide combination therapy in mHSPC and nmCRPC from the start of the database to 15 January 2026. The primary efficacy outcomes were overall survival and metastasis-free survival. Key safety outcomes included the total number of overall adverse events, the total number of grade ≥3 adverse events and serious adverse events, and the occurrence of specific adverse events of interest. The risk of bias was assessed by the Cochrane risk-of-bias tool for randomized trials (RoB 2). Publication bias was assessed by funnel plots. There were 8 research articles from 3 randomized clinical trials with 3,483 patients involved in this meta-analysis, including 1,509 nmCRPC patients from the ARAMIS trial, 1974 mHSPC patients from the ARASENS and ARANOTE trials. Combining darolutamide with ADT significantly prolonged overall survival (OS) and metastasis-free survival (MFS) in nmCRPC patients compared with placebo plus ADT. And darolutamide plus ADT with or without docetaxel also showed favorable overall survival in mHSPC patients. Subgroup meta-analyses of OS among mHSPC patients for baseline total PSA (tPSA) values and Gleason scores showed the beneficial efficacy of darolutamide in mHSPC. The addition of darolutamide in ADT and/or docetaxel did not lead to serious adverse events, like heart failure, bone fracture and hypertension, in both nmCRPC and mHSPC patients. Darolutamide combination therapy was beneficial to the prognosis and demonstrated a favorable safety profile in patients with advanced prostate cancer. Identifier CRD420251145736.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adverse events / Agonists / Androgen receptors / Androgens / Bias / Cancer therapies / Castration / Clinical trials / Combination therapy / Congestive heart failure / darolutamide / Medical prognosis / Meta-analysis / Metastases / Metastasis / metastasis-free survival / overall survival / Patients / Prostate cancer / Survival / Systematic Review