PhD Scientific Days 2026

Theoretical and Translational Medicine 1.

Comparative Effectiveness of Androgen Receptor Pathway Inhibitors in Metastatic Prostate Cancer: Large-Scale Evidence from Two Systematic Reviews and Meta-Analyses

Name of the presenter

Valikovics, Anikó Katalin

Institute/workplace of the presenter

Semmelweis University, Department of Urology and Translational medicine

Authors

Anikó Katalin valikovics¹, Anikó Katalin Valikovics², Dániel Bacsó^1,2, Nadeen Samaien², Isabel Pinto Amorim das Virgens², Mahmoud Obeidat², Boglárka Szentes², Gergely Agócs², Tamás Széll¹, Gergely Bánfi¹, Boris Hadaschik³, Péter Hegyi², Péter Nyirády¹, Tibor Szarvas^1,3
1: Semmelweis University Department of Urology
2: Semmelweis University Centre for Translational Medicine
3: Department of Urology, University of Duisburg-Essen and German Cancer Consortium

Text of the abstract

Introduction
Treatment of metastatic prostate cancer (mPC) has been transformed by androgen receptor pathway inhibitors (ARPIs), including abiraterone (ABI), enzalutamide (ENZA), and apalutamide (APA), which significantly improve survival in both hormone-sensitive (mHSPC) and castration-resistant (mCRPC) disease. However, the optimal choice among these agents remains unclear, as direct head-to-head randomized trials are lacking.
Aims
To address this clinically relevant gap, we performed systematic reviews and meta-analyses to compare the efficacy and safety of ARPI therapies in both mCRPC and mHSPC.
Methods
Two systematic reviews and meta-analyses were conducted following predefined PICO framework, PRISMA guidelines, and PROSPERO registration. PubMed, Embase, and Cochrane were searched. In mCRPC, ABI was compared with ENZA in 47 studies including 71,984 patients. In mHSPC, APA-, ABI-, and ENZA-based doublet therapies were compared in 17 real-world studies including 18,626 patients. The primary endpoint was overall survival (OS), while multiple secondary endpoints included PSA response, progression-related outcomes, grade ≥3 adverse events (AEs) and treatment discontinuation (TDC).
Results
In mCRPC, ENZA showed significantly improved OS compared with ABI (HR: 0.79; 95% CI: 0.71–0.87) and higher PSA50 response (OR: 1.82; 95% CI: 1.38–2.40), but was associated with higher rates of severe AEs and TDC, whereas major cardiovascular events were less frequent. In mHSPC, APA-based doublet therapy demonstrated superior OS compared with ABI (HR: 1.27; 95% CI: 1.09–1.47) and longer time to castration-resistant disease (HR: 1.40; 95% CI: 1.05–1.88), with improved PSA responses. No significant survival differences were observed between APA and ENZA or between ABI and ENZA.
Conclusion
These two meta-analyses together included data from more than 90,000 patients and provide comparative evidence for currently used ARPI therapies in mPC. The results suggest clinically meaningful differences between agents and support individualized treatment selection, highlighting the need for head-to-head randomized trials.
Funding
No external funding. IPAV was supported by the EKÖP-2024 New National Excellence Programme. The funder had no role in the study.