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Clinical Trial
. 2021 Sep:155:56-63.
doi: 10.1016/j.ejca.2021.06.016. Epub 2021 Aug 3.

Docetaxel and prednisone with or without enzalutamide as first-line treatment in patients with metastatic castration-resistant prostate cancer: CHEIRON, a randomised phase II trial

Orazio Caffo  1 , Cinzia Ortega  2 , Franco Nolè  3 , Donatello Gasparro  4 , Claudia Mucciarini  5 , Michele Aieta  6 , Vittorina Zagonel  7 , Roberto Iacovelli  8 , Ugo De Giorgi  9 , Gaetano Facchini  10 , Antonello Veccia  11 , Erica Palesandro  2 , Elena Verri  3 , Sebastiano Buti  4 , Giorgia Razzini  5 , Giovanni Bozza  6 , Marco Maruzzo  7 , Chiara Ciccarese  8 , Giuseppe Schepisi  9 , Sabrina Rossetti  10 , Francesca Maines  11 , Stefania Kinspergher  11 , Lucia Fratino  12 , Paola Ermacora  13 , Maurizio Nicodemo  14 , Monica Giordano  15 , Donata Sartori  16 , Daniela Scapoli  17 , Roberto Sabbatini  18 , Giovanni Lo Re  19 , Franco Morelli  20 , Alessandro D'Angelo  21 , Isabella Vittimberga  22 , Paolo Lippe  23 , Francesco Carrozza  24 , Caterina Messina  25 , Luca Galli  26 , Francesca Valcamonico  27 , Camillo Porta  28 , Giovanni Pappagallo  29 , Massimo Aglietta  2
Affiliations
Clinical Trial

Docetaxel and prednisone with or without enzalutamide as first-line treatment in patients with metastatic castration-resistant prostate cancer: CHEIRON, a randomised phase II trial

Orazio Caffo et al. Eur J Cancer. 2021 Sep.

Abstract

Background: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC).

Methods: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m2, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration.

Results: The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%).

Conclusions: The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit.

Trial registration numbers: EudraCT 2014-000175-43 - NCT02453009.

Keywords: Chemo-hormonal therapy; Combination therapy; Docetaxel; Enzalutamide; Metastatic castration-resistant prostate cancer.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Orazio Caffo is an advisor to Janssen, MSD and Bayer, and a speaker for Astellas, AstraZeneca, Bayer, Janssen, MSD, Pfizer and Sanofi. Cinzia Ortega is an advisor to Janssen, Astellas, Pfizer, Novartis and MSD, and a speaker for MSD, BMS and Sanofi. Donatello Gasparro is a speaker for and an advisor to Sanofi and Astellas. Vittorina Zagonel is an advisor to Bristol-Myers Squibb, MSD, Eisai and Italfarmaco, and a speaker for Roche, Bristol-Myers Squibb, Astellas Pharma, Servier, AstraZeneca, MSD, Janssen and Ipsen. Roberto Iacovelli is an advisor to Pfizer, Ipsen, Janssen, Astellas, MSD and BMS. Ugo De Giorgi is a consultant of Astellas Pharma, Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche and Sanofi. Elena Verri is an advisor to Astellas, Bayer, Janssen and Sanofi. Sebastiano Buti is a speaker for and advisor to BMS, Pfizer, Pierre-Fabre, MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca and Novartis. Marco Maruzzo is an advisor to Pfizer, BMS, Janssen, MSD, Merck Serono and Ipsen. Giovanni Pappagallo is a counsellor and trainer for Astellas, AstraZeneca, Daiichi-Sankyo, Ipsen, Janssen, MSD, Pierre Fabre, Pfizer, Roche, Servier and Teva. Massimo Aglietta is an advisor to Bayer, BMS, Merck and Novartis, and has received travel support from BMS, Merck and Tesaro. Maurizio Nicodemo is a speaker for and an advisor to Bristol-Myers Squibb, Ipsen, Molteni and Janssen. Roberto Sabbatini is an advisor to Janssen, and a speaker for Astellas, Janssen and Sanofi. Franco Morelli is a speaker for MSD and Pfizer. Francesco Carrozza is a speaker for Janssen. Camillo Porta is a consultant of and speaker for Angelini, AstraZeneca, Bristol-Myers Squibb, Eisai, EUSA, General Electric, Ipsen, Merck, MSD, Novartis and Pfizer; an expert witness for EUSA and Pfizer; a member of the Protocol Steering Committee of Bristol-Myers Squibb, Eisai and EUSA and has received travel support from Roche. The remaining authors have no conflict of interest to be declared

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