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.
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Date
2016-04-01ICR Author
Author
James, ND
Pirrie, SJ
Pope, AM
Barton, D
Andronis, L
Goranitis, I
Collins, S
Daunton, A
McLaren, D
O'Sullivan, J
Parker, C
Porfiri, E
Staffurth, J
Stanley, A
Wylie, J
Beesley, S
Birtle, A
Brown, J
Chakraborti, P
Hussain, S
Russell, M
Billingham, LJ
Type
Journal Article
Metadata
Show full item recordAbstract
IMPORTANCE: Bony metastatic 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 bony metastatic 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. TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN12808747.
Collections
Subject
Humans
Prostatic Neoplasms
Strontium
Taxoids
Diphosphonates
Imidazoles
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Proportional Hazards Models
Drug Resistance, Neoplasm
Aged
Middle Aged
Male
Kaplan-Meier Estimate
Docetaxel
Zoledronic Acid
Research team
Prostate and Bladder Cancer Research
Language
eng
Date accepted
2015-11-06
License start date
2016-04
Citation
JAMA oncology, 2016, 2 (4), pp. 493 - 499
Publisher
AMER MEDICAL ASSOC