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

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.

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

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).

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.

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.

European journal of cancer (Oxford, England : 1990). 2022 Aug 11 [Epub ahead of print]

Chiara Ciccarese, Roberto Iacovelli, Cora N Sternberg, Silke Gillessen, Giampaolo Tortora, Karim Fizazi

Medical Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy., Medical Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy. Electronic address: ., Englander Institute for Precision Medicine, Weill Cornell Department of Medicine, Sandra and Edward Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY, USA., Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), 6500 Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), 6900 Lugano, Switzerland; Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK., Medical Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy; Faculty of Medicine, Università Cattolica del Sacro Cuore, Rome, Italy., Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.

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