Clinical outcomes in patients with castrate-refractory prostate cancer (CRPC) metastatic to bone randomized in the factorial TRAPEZE trial to docetaxel (D) with strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747).

Genitourinary (Prostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Prostate) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA5000)
Nicholas David James, Sarah Pirrie, Darren Barton, Janet Elizabeth Brown, Lucinda Billingham, Stuart I. Collins, Adam Daunton, Alison J. Birtle, Prabir Ranjan Chakraborti, Daniel Ford, Syed A. Hussain, Helen Jones, Ann Pope, Emilio Porfiri, John Martin Russell, Andrew Stanley, John Staffurth, Duncan McLaren, Chris Parker, James Wylie; Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, Birmingham, United Kingdom; Cancer Research UK Experimental Cancer Medicine Centres, Leeds and Sheffield, United Kingdom; Cancer Research Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom; Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom; West Midlands Strategic Health Authority, Birmingham, United Kingdom; Rosemere Cancer Centre, Royal Preston Hospital, Preston, United Kingdom; Derby Royal Hospital, Derby, United Kingdom; Queen Elizabeth Hospital, Birmingham, United Kingdom; University of Liverpool, Liverpool, United Kingdom; University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom; School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom; Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; City Hospital, Birmingham, United Kingdom; Velindre Cancer Centre, Cardiff, United Kingdom; Department of Oncology, Edinburgh Cancer Centre, Edinburgh, United Kingdom; The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom

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Abstract Disclosures


Background: Bony metastatic CRPC has a poor prognosis and high morbidity. TRAPEZE is a factorial RCT using three agents, D, ZA, and Sr89. All have palliative benefits and are used in bony metastatic CRPC to control bone symptoms and (for D) to prolong survival. ZA was approved on the basis of reducing skeletal related events (SRE). Sr89 was approved to control pain from metastases and to reduce the need for subsequent bone treatments. ZA is commonly combined with D in practice but evidence that the combination is effective is lacking and costs considerable. Sr89 is generally used as a palliative therapy in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine clinical and cost-effectiveness scheduling. Methods: Patients were randomised to receive 6 cycles of D plus prednisolone: alone; with ZA; with a single dose of Sr89 after cycle 6 or both. Primary outcomes were clinical progression-free survival (CPFS: pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE free interval (SREFI); total SREs, and overall survival (OS). The log rank test and Cox regression modelling were used to determine clinical effectiveness. Results: TRAPEZE randomised 757 patients; median age 68.7 yrs; ECOG 0: 40% 1: 52% 2: 8%; prior RT 45%; median PSA 144 (IQR 51, 354). Provisional stratified log rank analysis of CPFS did not reach statistical significance for either agent (Sr89 p=0.11, ZA p=0.45). Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (HR=0.845; 95%CI 0.72, 0.99, p=0.036) and confirmed no effect of ZA (p=0.46). ZA did show a significant effect on SREFI (HR=0.76; 95%CI 0.63, 0.93, p=0.008). There was no effect of either agent on overall survival (Sr89 p=0.74, ZA p=0.91). Conclusions: Sr89 after six cycles of docetaxel improved CPFS but not OS. ZA did not improve CPFS or OS but did significantly improve median SREFI, mostly post progression, suggesting a role as post chemotherapy maintenance therapy. Further health economic and QoL analyses are pending. Clinical trial information: 12808747.