• Pernelle Lavaud, Gwenaëlle Gravis, Stéphanie Foulon, Florence Joly, Stéphane Oudard, Frank Priou, Igor Latorzeff, Loïc Mourey, Michel Soulié, Remy Delva, Ivan Krakowski, Brigitte Laguerre, Christine Théodore, Jean Marc Ferrero, Philippe Beuzeboc, Muriel Habibian, Frédéric Rolland, Gael Deplanque, Damien Pouessel, Sylvie Zanetta, Jean François Berdah, Jerome Dauba, Marjorie Baciuchka, Christian Platini, Claude Linassier, Nicole Tubiana-Mathieu, Jean Pascal Machiels, Kouri Claude El CE Medical Oncology Department, Centre Catherine de Sienne, Nantes, France., Alain Ravaud, Etienne Suc, Jean Christophe Eymard, Ali Hasbini, Guilhem Bousquet, Stéphane Culine, Jean-Marie Boher, Gabrielle Tergemina-Clain, Clémence Legoupil, and Karim Fizazi.
• Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
• Eur. Urol. 2018 May 1; 73 (5): 696-703.

BackgroundAndrogen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.ObjectiveTo investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC.Design, Setting, And ParticipantsRetrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC.Outcome Measurements And Statistical AnalysisFor the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance.Results And LimitationsOverall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel (p=0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6-7.7) and 4.1 mo (95% confidence interval: 1.3-4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel (p=0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3-4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups.ConclusionsDocetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients.Patient SummaryRechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting.Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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