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)
Research output: Contribution to journal › Article › peer-review
- Cancer Research UK Experimental Cancer Medicine Centres, Leeds and Sheffield, 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.
- Centre for Clinical Haematology
- University of Liverpool
- University Hospitals Birmingham NHS Foundation Trust
- Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
- University of Birmingham Centre for Cardiovascular Sciences, 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.
- Cancer Research Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
LBA5000 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.
|Journal||Journal of Clinical Oncology|
|Publication status||Published - 20 Jun 2013|
|Event||2013 ASCO Annual Meeting - McCormick Place, Chicago, United States|
Duration: 31 May 2013 → 4 Jun 2013
- Journal Article