Clinical outcomes and survival following treatment of metastatic castrate-refractory prostate cancer with docetaxel alone or with strontium-89, zoledronic acid, or both. The TRAPEZE randomized clinical trial

Nicholas D. James*, Sarah J. Pirrie, Ann M. Pope, Darren Barton, Lazaros Andronis, Ilias Goranitis, Stuart Collins, Adam Daunton, Duncan McLaren, Joe O'Sullivan, Christopher Parker, Emilio Porfiri, John Staffurth, Andrew Stanley, James Wylie, Sharon Beesley, Alison Birtle, Janet Brown, Prabir Chakraborti, Syed HussainMartin Russell, Lucinda J. Billingham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Importance: Bonymetastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival. 


Objective: To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bonymetastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival. 


Design, Setting, and Participants: The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months. 


Interventions: Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89. 


Main Outcomes and Measures: Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression-free interval, total SREs, and overall survival (OS). 


Results: Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95%CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95%CI, 0.85-1.14; P = .81); ZA had a significant effect on SRE-free interval (HR, 0.78; 95%CI, 0.65-0.95; P = .01). For OS, there was no effect of either Sr89 (HR, 0.92; 95%CI, 0.79-1.08; P = 0.34) or ZA (HR, 0.99; 95%CI, 0.84-1.16; P = 0.91). 


Conclusions and Relevance: Strontium-89 combined with docetaxel improved CPFS but did not improve OS, SRE-free interval, or total SREs; ZA did not improve CPFS or OS but did significantly improve median SRE-free interval and reduced total SREs by around one-third, suggesting a role as postchemotherapy maintenance therapy.

Original languageEnglish
Pages (from-to)493-499
Number of pages7
JournalJAMA oncology
Volume2
Issue number4
Early online date21 Jan 2016
DOIs
Publication statusPublished - Apr 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright 2016 American Medical Association. All rights reserved.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Clinical outcomes and survival following treatment of metastatic castrate-refractory prostate cancer with docetaxel alone or with strontium-89, zoledronic acid, or both. The TRAPEZE randomized clinical trial'. Together they form a unique fingerprint.

Cite this