Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2022 Sep:173:276-284.
doi: 10.1016/j.ejca.2022.07.011. Epub 2022 Aug 11.

Triplet therapy with androgen deprivation, docetaxel, and androgen receptor signalling inhibitors in metastatic castration-sensitive prostate cancer: A meta-analysis

Chiara Ciccarese  1 , Roberto Iacovelli  2 , Cora N Sternberg  3 , Silke Gillessen  4 , Giampaolo Tortora  5 , Karim Fizazi  6
Affiliations
Meta-Analysis

Triplet therapy with androgen deprivation, docetaxel, and androgen receptor signalling inhibitors in metastatic castration-sensitive prostate cancer: A meta-analysis

Chiara Ciccarese et al. Eur J Cancer. 2022 Sep.

Abstract

Background: The addition of either docetaxel or an androgen receptor signalling pathway inhibitor (ARSi) to androgen-deprivation therapy (ADT) has become the standard of care for metastatic castration-sensitive prostate cancer (mCSPC) patients. Recent phase III data support even greater survival impact of a triplet regimen with ADT plus docetaxel plus an ARSi (abiraterone or darolutamide) compared to ADT plus docetaxel.

Objective: To evaluate whether the addition of an ARSi to ADT improves outcomes of mCSPC patients treated with docetaxel.

Methods: We searched MEDLINE/PubMed, the Cochrane Library, and ASCO Meeting abstracts for randomised clinical trials (RCTs) testing the combination of ARSi + ADT in mCSPC men who received docetaxel. Data extraction was conducted according to the PRISMA statement. Summary hazard ratio (HR) was calculated using random- or fixed-effects models. The statistical analyses were performed with RevMan software (v.5.2.3).

Results: Five RCTs were selected. Triplet therapy improved overall survival (OS) compared to ADT + docetaxel in mCSPC patients (HR = 0.73; p < 0.00001). This intensified strategy maintained the OS benefit when the ARSi was administered concomitant to chemotherapy (HR = 0.72; p < 0.00001), but no statistical effect was detected if the ARSi was sequential to docetaxel (p = 0.44). Moreover, in the subgroup of men with de novo mCSPC, triplets significantly improved OS (HR = 0.72, p < 0.0001). The lack of access to raw data was the main limit of our analysis.

Conclusion: Our results support a clear survival advantage of adding an ARSi to ADT in mCSPC patients treated with docetaxel, mainly when the ARSi was administered concomitantly to chemotherapy and in the subgroup of de novo mCSPC.

Keywords: ARSi; Docetaxel; Metastatic castration-sensitive prostate cancer; Triplet therapy; mCSPC.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement Chiara Ciccarese: occasional consultant of IPSEN, Jannssen, MSD, Merck, Pfizer, Astellas. Roberto Iacovelli: advisory board member for Astellas, BMS, EISAI, IPSEN, Janssen, MSD, Novartis, Pfizer, Sanofi. Consultant for Astellas, EISAI, MSD, Pfizer. Cora N. Sternberg: Served as a consultant for Astellas Pharma, Sanofi–Genzyme, Roche-Genentech, Novartis, Bayer, Pfizer, Merck, MSD, AstraZeneca, Immunomedics (now Gilead), Janssen, Foundation Medicine, Impact Pharma, UroToday and Medscape. Silke Gillessen: Prof Silke Gillessen received (last 3 years) personal honoraria for participation in advisory boards from Amgen, MSD, Orion; other honoraria from Radio-televisione Svizzera Italiana (RSI), German-speaking European School of Oncology (DESO); invited speaker for ESMO, Swiss group for Clinical Cancer Research (SAKK), Swiss Academy of Multidisciplinary oncology (SAMO), Orikata academy research group, China Anti-Cancer Association Genitourinary Oncology Committee (CACA-GU); Speaker's bureau for Janssen Cilag; travel grant from ProteoMEdiX. Institutional honoraria for participation in advisory boards or in Independent Data Monitoring Committees and Steering Committees from AAA International, Amgen, Bayer, Bristol-Myers Squibb, Modra Pharmaceuticals, MSD, Novartis, Orion, Pfizer, Roche, Telixpharma Tolero Pharmaceutcials; other honoraria from Silvio Grasso Consulting. Patent royalties and other intellectual property for a research method for biomarker WO2009138392. Giampaolo Tortora: advisory board member for BMS and Novartis. Karim Fizazi: Participation to advisory boards and talks for: Amgen, Astellas, Astrazeneca, Bayer, Clovis, Janssen, MSD, Novartis/AAA, Pfizer, Sanofi Honoraria go to Gustave Roussy, my institution. Participation to advisory boards with personal honorarium for CureVac and Orion.

Publication types

MeSH terms

LinkOut - more resources