Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study | Clinical Pharmacy and Pharmacology | JAMA Oncology | JAMA Network
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Original Investigation
January 2017

Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study

Author Affiliations
  • 1Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam, the Netherlands
  • 2US Oncology Research, Houston, Texas
  • 3Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada
  • 4Yale Cancer Center, Division of Oncology, Department of Medicine, New Haven, Connecticut
  • 5NSHI Dorozhnaya Clinical Hospital of OAO Russian Railways, Rostov-on-Don, Russia
  • 6Department of Uro-Oncology, Centrum Onkologii – Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland
  • 7San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy
  • 8Texas Oncology, Austin
  • 9University Hospital del Mar-IMIM, Barcelona, Spain
  • 10Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • 11Rocky Mountain Cancer Centers, Aurora, Colorado
  • 12Catalan Institute of Oncology, Department of Medical Oncology, Barcelona, Spain
  • 13Department of Clinical Oncology, The Christie NHS Foundation Trust and Institute of Cancer Sciences, University of Manchester, Manchester, England
  • 14Department of Urology, Rechts der Isar Medical Center, Technische Universität München, München, Germany
  • 15State Institution of Healthcare “ Regional Clinical Oncology Dispensary”, Omsk, Russia
  • 16Centre Léon Bérard, Department of Medical Oncology, Lyon, France
  • 17Department of Clinical Oncology, Royal Marsden Hospital, London, England
  • 18Medical Oncology Department, Groupe Hospitalier Universitaire Caremeau Place du Professeur Robert Debré, Nîmes, France
  • 19Celgene Corporation, Summit, New Jersey
JAMA Oncol. 2017;3(1):68-75. doi:10.1001/jamaoncol.2016.3000
Key Points

Question  Is the total number of docetaxel cycles administered to patients with metastatic castration resistant prostate cancer an independent prognostic factor for overall survival (OS)?

Findings  In a post hoc analysis of the Mainsail study, it was found that the total number of docetaxel cycles delivered is an independent factor for OS. Patients who received more than 10 cycles of docetaxel had a higher median OS compared with patients treated with 8 to 10 cycles or patients treated with 5 to 7 cycles.

Meaning  These findings suggest that the total number of docetaxel cycles administered to patients with metastatic castration resistant prostate cancer contributes to OS.

Abstract

Importance  The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles.

Objective  To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial.

Design, Setting, and Participants  The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors.

Main Outcomes and Measures  Total number of docetaxel cycles delivered as an independent factor for OS.

Results  Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P < .001), irrespective of lenalidomide treatment (HR, 1.060; 95% CI, 0.924-1.215; P = .41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P < .001).

Conclusions and Relevance  These findings suggest that continuation of docetaxel chemotherapy contributes to the survival benefit. Prospective validation is warranted.

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