title: Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial.
abstract: The role of chemotherapy in metastatic non castrate prostate cancer (mNCPC) is debated. Survival benefits of docetaxel (D) added to androgen-deprivation therapy (ADT) were shown in the CHAARTED trial in patients with metastatic high-volume disease (HVD).
  
  
  
  To assess the impact of metastatic burden and to update overall survival (OS) data of the GETUG-AFU15 study.
  
  
  
  Randomized phase 3 trial of ADT plus D versus ADT alone in 385 mNCPC patients; median follow-up of 7 yr.
  
  
  
  Primary end point was OS. Secondary end points were biochemical progression-free survival (bPFS) and radiographic progression-free survival (rPFS). Retrospective analysis was by tumor volume.
  
  
  
  After a median follow-up of 83.9 mo, median OS in the overall population was 62.1 mo (95% confidence interval [CI], 49.5-73.7) and 48.6 mo (95% CI, 40.9-60.6) for ADT plus D and ADT arms, respectively (hazard ratio [HR]: 0.88 [95% CI, 0.68-1.14]; p=0.3). Median OS in ADT plus D and ADT arms, respectively, was for HVD patients: 39.8 mo (95% CI, 28.0-53.4) versus 35.1 mo (95% CI, 29.9-43.6) (HR: 0.78 [95% CI, 0.56-1.09]; p=0.14), for low-volume disease (LVD) patients; median was not reached (NR; 95% CI, 69.5-NR) and 83.4 mo (95% CI, 61.8-NR) (HR: 1.02 [95% CI, 0.67-1.55]; p=0.9). For upfront metastatic patients, OS was 52.6 mo (95% CI, 43.3-66.8) and 41.5 mo (95% CI, 36.3-54.5), respectively (HR: 0.93 [95% CI, 0.69-1.25]; p=0.6). The bPFS (HR: 0.73 [95% CI, 0.56-0.94]; p=0.014) and rPFS (HR: 0.75 [95% CI, 0.58-0.97]; p=0.030) were significantly longer in the ADT plus D arm. Limitations included the retrospective analysis of metastatic extent and the lack of statistical power to detect a significant difference in subgroups.
  
  
  
  The post hoc analyses of the GETUG-AFU15 study demonstrated a nonsignificant 20% reduction in the risk of death in the HVD subgroup. Patients with LVD had no survival improvement with early D.
  
  
  
  In this study, docetaxel added to castration did not improve survival in patients with metastatic hormone-sensitive prostate cancer, partly due to methodological issues. However, early chemotherapy should be discussed with all patients, given the data of three randomized trials including GETUG-AFU15.
authors.affiliation: Medical Oncology, Institut Paoli-Calmettes, Marseille, France. Electronic address: gravisg@ipc.unicancer.fr.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Gravis
authors.affiliation: Biostatistics, Institut Paoli-Calmettes, Marseille, France; Aix-Marseille Université, UMR_S 912 (SESSTIM), IRD, Marseille, France; INSERM, UMR_S 912 (SESSTIM), Marseille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boher
authors.affiliation: Medical Oncology, Centre François Baclesse - CHU Côte de Nacre, Caen, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.affiliation: Urology Department, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Soulié
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Medical Oncology, Centre Hospitalier Les Oudairies, La Roche-sur-Yon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Priou
authors.affiliation: Radiotherapy Department, Clinique Pasteur, Toulouse, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Latorzeff
authors.affiliation: Department of Medical Oncology, Centre Paul Papin, Angers, France.
authors.forename: Remy
authors.initials: R
authors.lastname: Delva
authors.affiliation: Medical Oncology, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Krakowski
authors.affiliation: Medical Oncology, Centre Eugène Marquis, Rennes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laguerre
authors.affiliation: Medical Oncology, Centre René Gauducheau, Saint-Herblain, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rolland
authors.affiliation: Medical Oncology, Hôpital Foch, Suresnes, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Théodore
authors.affiliation: Medical Oncology, Groupe Hospitalier Saint Joseph, Paris, France.
authors.forename: Gael
authors.initials: G
authors.lastname: Deplanque
authors.affiliation: Medical Oncology, Centre Antoine Lacassagne, Nice, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ferrero
authors.affiliation: Medical Oncology, Hôpital Saint-Louis, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Culine
authors.affiliation: Institut Claudius Régaud, Toulouse, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Mourey
authors.affiliation: Medical Oncology, Institut Curie, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Beuzeboc
authors.affiliation: UNICANCER, Paris, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Habibian
authors.affiliation: Medical Oncology Department, Georges Pompidou Hospital and René Descartes University, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000473:pathology / Q000517:prevention & control; D009367:Neoplasm Staging; D010043:Outcome and Process Assessment, Health Care; D011467:Prostate / Q000000981:diagnostic imaging / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy; D011859:Radiography / Q000379:methods; D043823:Taxoids / Q000008:administration & dosage*; D047368:Tumor Burden
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel
keywords: Androgen deprivation therapy; Docetaxel; Metastatic noncastrate prostate cancer; Metastatic volume