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Original Investigation
January 31, 2019

Effect of Adding Docetaxel to Androgen-Deprivation Therapy in Patients With High-Risk Prostate Cancer With Rising Prostate-Specific Antigen Levels After Primary Local Therapy: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris, France
  • 2Department of Oncology Radiotherapy, Clinique Pasteur, Toulouse, France
  • 3Department of Medical Oncology, Centre Galilée, Hôpital Privé la Louvière, Lille, France
  • 4Department of Oncology Radiotherapy, Centre Hospitalier Privé St Grégoire, Rennes, France
  • 5Department of Medical Oncology, Centre François Baclesse, Caen, France
  • 6Department of Medical Oncology, Hôpital Privé des Côtes d'Armor, Plérin, France
  • 7Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Angers, France
  • 8Department of Medical Oncology, Institut de Cancérologie de l'Ouest, St Herblain, France
  • 9Department of Medical Oncology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
  • 10Department of Medical Oncology, Centre Hospitalier de Vendée, La Roche sur Yon, France
  • 11Department of Medical Oncology, Institut Curie, Paris, France
  • 12Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France
  • 13Department of Medical Oncology, Centre Hospitalier Bretonneau, Tours, France
  • 14Department of Oncology Radiotherapy, Centre Joliot Curie, Rouen, France
  • 15Department of Medical Oncology, Clinique Victor Hugo, Institut Inter-régional de Cancérologie, Le Mans, France
  • 16Department of Oncology Radiotherapy, Hôpital de la Timone, Marseille, France
  • 17Department of Medical Oncology, Centre Hospitalier Versailles André Mignot, Le Chesnay, France
  • 18Department of Medical Oncology, Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania
  • 19Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France
  • 20Department of Medical Oncology, Hôpital St Andre, Bordeaux, France
  • 21Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre Les Nancy, France
  • 22Department of Medical Oncology, Hôpital Henri Mondor, Creteil, France
  • 23Department of Medical Oncology, Fondation Hopital St Joseph, Paris, France
  • 24Department of Medical Oncology, Centre Hospitalier de Compiegne, Compiegne, France
  • 25Department of Medical Oncology, Hôpital Foch, Suresnes, France
  • 26Department of Medical Oncology, Institut Bergonie, Bordeaux, France
  • 27Department of Medical Oncology, Hôpital St Louis, Paris, France
  • 28Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie, Paris, France
JAMA Oncol. 2019;5(5):623-632. doi:10.1001/jamaoncol.2018.6607
Key Points

Question  Is the combination of androgen-deprivation therapy plus docetaxel superior to androgen-deprivation therapy alone in the treatment of nonmetastatic prostate cancer in patients with increasing prostate-specific antigen levels after primary local therapy?

Findings  In this phase 3 randomized clinical trial including 254 patients, there was no significant difference between treatments for the primary outcome measure, prostate-specific antigen progression-free survival (median follow-up, 30.0 months). In addition, no significant difference was noted in the secondary outcome measures of radiologic progression-free survival and overall survival (median follow-up, 10.5 years).

Meaning  Addition of docetaxel to androgen-deprivation therapy seems to be unwarranted in patients with high-risk prostate cancer without metastases in the absence of better predictors of risk for metastatic disease.

Abstract

Importance  Androgen-deprivation therapy (ADT) plus docetaxel is the standard of care in hormone-naive metastatic prostate cancer but is of uncertain benefit in a nonmetastatic, high-risk prostate cancer setting.

Objective  To assess the benefit of ADT plus docetaxel in patients presenting with rising prostate-specific antigen (PSA) levels after primary local therapy and high-risk factors but no evidence of metastatic disease.

Design, Setting, and Participants  This open-label, phase 3, randomized superiority trial comparing ADT plus docetaxel vs ADT alone enrolled patients from 28 centers in France between June 4, 2003, and September 25, 2007; final follow-up was conducted April 12, 2017, and analysis was performed May 2 to July 31, 2017. Patients had undergone primary local therapy for prostate cancer, were experiencing rising PSA levels, and were considered to be at high risk of metastatic disease. Stratification was by prior local therapy and PSA-level doubling time (≤6 vs >6 months), and intention-to-treat analysis was used.

Interventions  Patients were randomly assigned to receive ADT (1 year) plus docetaxel, 70 mg/m2 (every 3 weeks [6 cycles]), or ADT alone (1 year).

Main Outcomes and Measures  The primary outcome was PSA progression-free survival (PSA-PFS). Secondary end points were PSA response, radiologic PFS, overall survival, safety, and quality of life.

Results  Overall, 254 patients were randomized (1:1) to the trial; median age, 64 years in the ADT plus docetaxel arm, 66 years in the ADT alone arm. At a median follow-up of 30.0 months, the median PSA-PFS was 20.3 (95% CI, 19.0-21.6) months in the ADT plus docetaxel arm vs 19.3 (95% CI, 18.2-20.8) months in the ADT alone arm (hazard ratio [HR], 0.85; 95% CI, 0.62-1.16; P = .31). At a median follow-up of 10.5 years, there was no significant between-arm difference in radiologic PFS (HR, 1.03; 95% CI, 0.74-1.43; P = .88). Overall survival data were not mature. The most common grade 3 or 4 hematologic toxic effects in the ADT plus docetaxel arm were neutropenia (60 of 125 patients [48.0%]), febrile neutropenia (10 [8.0%]), and thrombocytopenia (4 [3.0%]). There was no significant between-arm difference in overall quality of life.

Conclusions and Relevance  Compared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA-PFS in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease.

Trial Registration  French Health Products Safety Agency identifier: 030591; ClinicalTrials.gov identifier: NCT00764166

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