Androgen 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.
To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC.
Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC.
For 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.
Overall, 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.
Docetaxel 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.
Rechallenging 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.
European urology. 2017 Oct 23 [Epub ahead of print]
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, Claude El Kouri, Alain Ravaud, Etienne Suc, Jean Christophe Eymard, Ali Hasbini, Guilhem Bousquet, Stéphane Culine, Jean-Marie Boher, Gabrielle Tergemina-Clain, Clémence Legoupil, Karim Fizazi
Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Institut Paoli Calmette, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Marseille University, UM 105, F-13284, Marseille, France., Department of Clinical Research and Investigation, Biostatistics and Methodology Unit, Institut Gustave Roussy, Villejuif, France., Oncology Department, Centre François Baclesse, Caen, France., Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France., Department of Oncology, Centre hospitalier départemental Les Oudairies, La Roche-sur-Yon, France., Department of Radiotherapy, Groupe ONCORAD Garonne and Clinique Pasteur, Toulouse, France., Department of Oncology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France., Department of Urology, Andrology and Transplantation, Centre Hospitalier Universitaire Toulouse-Rangueil, Toulouse, France., Department of Medical Oncology, Paul Papin Cancer Centre, Angers, France., Department of Oncology, Centre Bergonié, Bordeaux, France., Department of Medical Oncology, Centre Eugène Marquis, Rennes, France., Department of Medical Oncology, Hopital Foch, Suresnes, France., Department of Medical Oncology, Antoine Lacassagne Cancer Centre, Nice, France., Department of Medical Oncology, Curie Institute, Paris, France., R&D Unicancer, Paris, France., Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Saint Herblain, France., Department of Medical Oncology, Hopital Riviera-Chablais, Vaud-Valais - Vevey, Switzerland., Department of Medical Oncology, Institut Claudius Rigaud, Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France., Medical Oncology Department, Centre Georges-François Leclerc, Dijon, France., Medical Oncology Department, Clinique Sainte Marguerite, Hyeres, France., Medical Oncology Department, Hôpital Layné, Mont de Marsan, France., Medical Oncology Department, Centre Hospitalier La Timone, Marseille, France., Medical Oncology Department, Centre Régional Hospitalier, Metz-Thionville, France., Medical Oncology Department, Hôpital Bretonneau, Tours, France., Medical Oncology Department, Centre Hospitalier Dupuytren, Limoges, France., Institut Roi Albert II, Service d'Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium., Medical Oncology Department, Centre Catherine de Sienne, Nantes, France., Medical Oncology Department, Hôpital Saint-André, Bordeaux, France., Medical Oncology Department, Clinique Saint-Jean Languedoc, Toulouse, France., Medical Oncology Department, Institut Jean Godinot, Reims, France., Medical Oncology Department, Clinique Armoricaine de Radiologie, Saint Brieuc, France., Medical Oncology Department, Hôpital Avicenne, Bobigny, France., Medical Oncology Department, Hôpital Saint Louis, Paris, France., Department of Clinical Research and Investigation, Biostatistics, and Methodology Unit, Institut Paoli Calmettes, Marseille, France., Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address: .