SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Genitourinary Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1468928
A network meta-analysis of the safety of systemic treatments in patients with metastatic hormone-sensitive prostate cancer
Provisionally accepted
Massimo Di Maio1*
Enrique Gonzalez-Billalabeitia2
Laura Marandino3
Pablo Maroto4Marc-Olivier Timsit5Irene Luccarini6
Paul Robinson7
Suzy Van Sanden8Boris A. Hadaschik9- 1University of Turin, Turin, Italy
- 2Hospital Universitario 12 de Octubre, Madrid, Spain
- 3San Raffaele Scientific Institute (IRCCS), Milan, Lombardy, Italy
- 4Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- 5Hôpital Européen Georges-Pompidou, Paris, France
- 6Janssen Cilag S.p.A, Milan, Italy
- 7Janssen-Cilag Ltd, High Wycombe, United Kingdom
- 8Janssen Pharmaceutica NV, Beerse, Belgium
- 9University Hospital Essen, Essen, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: The last decade saw the emergence of several new systemic therapies for metastatic hormone-sensitive prostate cancer (mHSPC). While these treatments demonstrated similar efficacy in indirect comparisons, comparisons of safety outcomes are needed to help guide the selection of treatment regimens and sequences. We conducted network meta-analyses (NMAs) comparing safety of systemic treatments for mHSPC.Methods: A systematic literature review was performed for randomized controlled trials (RCTs) investigating systemic treatments for mHSPC published before July 2022. Studies were restricted by network connectivity and study population homogeneity. Bayesian NMAs were performed for available data on grade ≥3 adverse events (AEs), serious AEs (SAEs), and any AE. Results: The study included eight RCTs (n=172-1228 by treatment arm) and seven treatments regimens: androgen deprivation therapy (ADT) alone, docetaxel plus ADT, androgen receptor pathway inhibitor (ARPI; apalutamide, enzalutamide, or abiraterone acetate plus prednisone [AAP]) plus ADT, and docetaxel plus ARPI (darolutamide or AAP) plus ADT. Apalutamide plus ADT had the lowest relative risk ([RR]; 1.18 (95% credible interval [CrI] 1.02-1.35) of grade ≥3AEs versus ADT alone, followed by enzalutamide plus ), docetaxel plus ), AAP plus ), darolutamide plus docetaxel plus ), and AAP plus docetaxel plus ). For SAEs, RRs (95% CrI) versus ADT alone were 1.26 (1.03-1.53) for apalutamide plus ADT, for AAP plus ADT, for enzalutamide plus ADT, for docetaxel plus ADT, for darolutamide plus docetaxel plus ADT. Similar results were observed for any AE.Conclusions: Overall, risk of grade ≥3 AEs, SAEs, and any AE was lower with doublet ARPI versus docetaxel-based doublet or triplet regimens, and apalutamide plus ADT had the lowest risk. Variability of data reporting should be considered.
Keywords: adverse events, Androgen receptor pathway inhibitors, Metastatic castrationsensitive prostate cancer, Metastatic hormone-sensitive prostate cancer, serious adverse events, MHSPC
Received: 10 Feb 2025; Accepted: 08 Aug 2025.
Copyright: © 2025 Di Maio, Gonzalez-Billalabeitia, Marandino, Maroto, Timsit, Luccarini, Robinson, Van Sanden and Hadaschik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Massimo Di Maio, University of Turin, Turin, Italy
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.