Some Improvements in Survival, Skeletal Events Seen in Clinical Trial of Docetaxel Combo
Phase 3 results of the TRAPEZE trial of patients with bony metastatic castrate-refractory prostate cancer.
Phase 3 results of the TRAPEZE trial show combining zoledronic acid (ZA) with docetaxel improves skeletal-related events (SREs) in patients with bony metastatic castrate-refractory prostate cancer (CRPC) but not clinical progression-free survival (CPFS) or overall survival (OS); combining strontium-89 (Sr89) with docetaxel improved only CPFS. These results were published online ahead of print in the journal JAMA Oncology.1
Bony metastatic CRPC has a poor prognosis and high morbidity. Combination ZA and docetaxel is commonly used to treat these patients, but evidence on its effectiveness is lacking. Sr89 is used palliatively in patients who are not candidates for chemotherapy.
Phase 2 analysis of the TRAPEZE trial confirmed all 3 agents were safe and feasible in combination; in phase 3, researchers assessed the impact of the treatments on survival.
The researchers sought to determine clinical and cost effectiveness of 4 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.
Overall, 349 of 757 participants (46%), median age 68 years, completed docetaxel treatment. CPFS was not statistically significant with either Sr89 or ZA.
Cox regression analysis adjusted for all stratification variables showed improved CPFS with Sr89 (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P=.03) and confirmed ZA had no effect (HR, 0.98; 95% CI, 0.85-1.14; P=.81); however, a significant effect on SRE-free interval was seen with ZA (HR, 0.78; 95% CI, 0.65-0.95; P=.01). No effect on OS was seen with 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).
The findings demonstrate combining Sr89 with docetaxel improved CPFS but not OS, SRE-free interval, or total SREs. Combination docetaxel and ZA did not improve CPFS or OS, but significant improvement was seen in median SRE-free interval and an approximately one-third reduction in total SREs was observed. The researchers suggest ZA may have a role as postchemotherapy maintenance therapy.
1. James ND, Pirrie SJ, Pope AM, et al. 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 [published online ahead of print January 21, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2015.5570.