Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach

This article aims to critically evaluate the evidence for triplet therapy consisting of androgen deprivation therapy (ADT), docetaxel and a second-generation androgen receptor pathway inhibitor ([ARPI]; abiraterone, enzalutamide, darolutamide or apalutamide) in patients with metastatic hormone-sensi...

Full description

Saved in:
Bibliographic Details
Main Authors: Almudena Zapatero, Teresa Alonso-Gordoa, Alfredo Rodríguez Antolín, Felipe Couñago, Noelia Sanmamed, Mario Domínguez Esteban, Marta López Valcárcel, Ray Manneh, Ángel Borque-Fernando, Nuria Sala González, Pablo Maroto
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Oncology Reviews
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/or.2025.1599292/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849304133439324160
author Almudena Zapatero
Teresa Alonso-Gordoa
Alfredo Rodríguez Antolín
Felipe Couñago
Felipe Couñago
Noelia Sanmamed
Mario Domínguez Esteban
Marta López Valcárcel
Ray Manneh
Ángel Borque-Fernando
Nuria Sala González
Pablo Maroto
author_facet Almudena Zapatero
Teresa Alonso-Gordoa
Alfredo Rodríguez Antolín
Felipe Couñago
Felipe Couñago
Noelia Sanmamed
Mario Domínguez Esteban
Marta López Valcárcel
Ray Manneh
Ángel Borque-Fernando
Nuria Sala González
Pablo Maroto
author_sort Almudena Zapatero
collection DOAJ
description This article aims to critically evaluate the evidence for triplet therapy consisting of androgen deprivation therapy (ADT), docetaxel and a second-generation androgen receptor pathway inhibitor ([ARPI]; abiraterone, enzalutamide, darolutamide or apalutamide) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), and what this evidence reveals regarding the use of these treatments in clinical practice. A search of PubMed, Medline, Embase, Cochrane, Scopus and Web of Science was conducted in April 2024 to identify relevant prospective and retrospective observational trials, randomized controlled trials (RCTs) and meta-analyses. The search identified 52 relevant articles: six full articles and 31 abstracts based on three RCTs, one observational study and 14 meta-analyses. Abiraterone- or darolutamide-containing triplet therapy was significantly better than ADT + docetaxel for improving overall survival in all study populations, particularly subgroups with high-volume and/or synchronous disease. The tolerability of ADT + docetaxel and triplet therapy were similar with most adverse events related to docetaxel. There were no data comparing triplet therapy with ADT + ARPI doublet therapy. Triplet therapy appears to be the most effective first-line regimen for men with mHSPC, good performance status and high-volume and synchronous metastases. Darolutamide-based triplet therapy may also be of benefit in other patients with high- or low-risk disease. Careful consideration of the risks and benefits are required to determine which patients can be spared from receiving docetaxel and rather be treated with alternative regimens.
format Article
id doaj-art-cfc27a8810ab46388a8cf160cd52aebf
institution Kabale University
issn 1970-5557
language English
publishDate 2025-07-01
publisher Frontiers Media S.A.
record_format Article
series Oncology Reviews
spelling doaj-art-cfc27a8810ab46388a8cf160cd52aebf2025-08-20T03:55:48ZengFrontiers Media S.A.Oncology Reviews1970-55572025-07-011910.3389/or.2025.15992921599292Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approachAlmudena Zapatero0Teresa Alonso-Gordoa1Alfredo Rodríguez Antolín2Felipe Couñago3Felipe Couñago4Noelia Sanmamed5Mario Domínguez Esteban6Marta López Valcárcel7Ray Manneh8Ángel Borque-Fernando9Nuria Sala González10Pablo Maroto11Radiation Oncology Department, Health Research Institute, Hospital Universitario de La Princesa, Madrid, SpainMedical Oncology Department, Ramón y Cajal University Hospital, Madrid, SpainUrology Service, Hospital Universitario 12 de Octubre, Madrid, SpainGenesisCare Radiation Oncology Department, San Francisco de Asís University Hospital and Vithas La Milagrosa University Hospital, Madrid, SpainDepartment of Medicine, Faculty of Medicine, Health and Sport Sciences, Universidad Europea de Madrid, Madrid, SpainRadiation Oncology Department, Clínico San Carlos Hospital, Madrid, SpainUrology Service, Marqués de Valdecilla University Hospital, Santander, SpainRadiation Oncology Department, Puerta de Hierro Majadahonda University Hospital, Madrid, SpainSociety of Oncology and Hematology of Cesar, Valledupar, Colombia0Urology Service, Miguel Servet University Hospital, IIS-Aragón, Zaragoza, Spain1Medical Oncology Service, Catalan Institute of Oncology, Josep Trueta Hospital, Girona, Spain2Medical Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, SpainThis article aims to critically evaluate the evidence for triplet therapy consisting of androgen deprivation therapy (ADT), docetaxel and a second-generation androgen receptor pathway inhibitor ([ARPI]; abiraterone, enzalutamide, darolutamide or apalutamide) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), and what this evidence reveals regarding the use of these treatments in clinical practice. A search of PubMed, Medline, Embase, Cochrane, Scopus and Web of Science was conducted in April 2024 to identify relevant prospective and retrospective observational trials, randomized controlled trials (RCTs) and meta-analyses. The search identified 52 relevant articles: six full articles and 31 abstracts based on three RCTs, one observational study and 14 meta-analyses. Abiraterone- or darolutamide-containing triplet therapy was significantly better than ADT + docetaxel for improving overall survival in all study populations, particularly subgroups with high-volume and/or synchronous disease. The tolerability of ADT + docetaxel and triplet therapy were similar with most adverse events related to docetaxel. There were no data comparing triplet therapy with ADT + ARPI doublet therapy. Triplet therapy appears to be the most effective first-line regimen for men with mHSPC, good performance status and high-volume and synchronous metastases. Darolutamide-based triplet therapy may also be of benefit in other patients with high- or low-risk disease. Careful consideration of the risks and benefits are required to determine which patients can be spared from receiving docetaxel and rather be treated with alternative regimens.https://www.frontiersin.org/articles/10.3389/or.2025.1599292/fullandrogen deprivation therapyandrogen receptor-targeted therapydocetaxelhormone-sensitive prostate cancermetastatic prostate cancer
spellingShingle Almudena Zapatero
Teresa Alonso-Gordoa
Alfredo Rodríguez Antolín
Felipe Couñago
Felipe Couñago
Noelia Sanmamed
Mario Domínguez Esteban
Marta López Valcárcel
Ray Manneh
Ángel Borque-Fernando
Nuria Sala González
Pablo Maroto
Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach
Oncology Reviews
androgen deprivation therapy
androgen receptor-targeted therapy
docetaxel
hormone-sensitive prostate cancer
metastatic prostate cancer
title Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach
title_full Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach
title_fullStr Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach
title_full_unstemmed Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach
title_short Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach
title_sort triplet systemic therapy for hormone sensitive prostate cancer a critical review with a multidisciplinary approach
topic androgen deprivation therapy
androgen receptor-targeted therapy
docetaxel
hormone-sensitive prostate cancer
metastatic prostate cancer
url https://www.frontiersin.org/articles/10.3389/or.2025.1599292/full
work_keys_str_mv AT almudenazapatero tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT teresaalonsogordoa tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT alfredorodriguezantolin tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT felipecounago tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT felipecounago tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT noeliasanmamed tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT mariodominguezesteban tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT martalopezvalcarcel tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT raymanneh tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT angelborquefernando tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT nuriasalagonzalez tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach
AT pablomaroto tripletsystemictherapyforhormonesensitiveprostatecanceracriticalreviewwithamultidisciplinaryapproach