Addition of androgen-receptor pathway inhibitors to standard of care in metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis.

To evaluate activity, safety and nuances of androgen-receptor pathway inhibitors (ARPI) with standard-of-care therapy (SOC), i.e., androgen deprivation therapy (ADT) alone or with docetaxel, for metastatic hormone-sensitive prostate cancer (mHSPC). Several randomized clinical trials (RCTs) have evaluated different agents in this setting. We conducted a systematic review and meta-analysis to better define the benefits and risks of combining ARPI with SOC in mHSPC. A comprehensive literature search of MEDLINE/PubMed, Web of Science, Scopus, and meeting abstracts from the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was performed in April 2025. The study adhered to PRISMA guidelines for systematic reviews and meta-analyses. Overall survival (OS) was the primary endpoint, with progression-free survival (PFS), time-to-progression of pain and PSA, and safety as secondary endpoints. Summary hazard ratios (HRs) were calculated for survival outcomes, and risk ratios (RRs) for safety. Random- or fixed-effects models were applied based on study heterogeneity. Eight RCTs fulfilled the prespecified inclusion criteria. The combination of ARPI and SOC significantly improved OS (HR = 0.74; P < 0.00001) and PFS (HR = 0.50 for clinical PFS, HR = 0.49 for radiological PFS; P < 0.0001) compared to the SOC. The benefit was confirmed excluding docetaxel. We did not show heterogeneity among treatment efficacy and disease burden, onset timing or treatment strategy. Adverse events (AEs) were not increased after adding ARPI to SOC, except from hypertension and any grade cardiac AEs. This meta-analysis supports the addition of ARPI to SOC in mHSPC, significantly improving survival outcomes. Uncertainties persist regarding the role of triple therapies including docetaxel. Identifying prognostic and predictive biomarkers is critical to tailoring therapy for patients most likely to benefit from different approaches.