CHICAGO―Neither zoledronic acid (ZA) nor strontium-89 (Sr89) after six cycles of docetaxel improve overall survival among patients with castrate-refractory prostate cancer (CRPC), but Sr89 is associated with improved clinical progression-free survival (cPFS), report authors of a randomized TRAPEZE clinical scheduling and cost-effectiveness study presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.
“Sr89 after 6 cycles of docetaxel improved cPFS but not overall survival,” reported Nicholas David James, MD, PhD, of the Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, in Birmingham, UK, and coauthors.
The TRAPEZE trial compared the cPFS (pain progression, skeletal-related events [SRE] or death), cost-effectiveness, SRE-free interval, total SREs, and overall survival (OS) associated with combinations of palliative agents used for bony metastatic CRPC: docetaxel (D), Sr89, and ZA.
A total of 757 patients were randomly assigned to one of four treatment groups, to receive either six cycles of D plus prednisolone alone, or that regimen plus ZA or a single dose of Sr89 after cycle 6, or with both ZA and Sr89.
“cPFS did not reach statistical significance for either agent (Sr89 P=0.11, ZA P=0.45),” Dr. James reported.
After adjusting for Eastern Cooperative Oncology Group status, prostate-specific antigen age stratification variables, however, Sr89 was associated with a significant cPFS benefit (median cPFS 8.8 vs. 9.8 months; hazard ratio [HR], 0.845; 95% CI: 0.72-0.99; P=0.036) while confirming that ZA was not associated with a benefit (P=0.46).
OS rates were “disappointing,” Dr. James said. “There was no impact by ZA or Sr89 on median survival.”
SRE free interval periods were, not surprisingly, improved with ZA (13.1 vs. 18.1 months; HR, 0.7; 95% CI: 0.60-0.91; P=0.005).
“With Sr89, somewhat surprisingly, given the effects on the primary outcome, there was less effect on SRE free interval” (median 14.7 vs. 16.4 months; HR, 0.91; 95% CI: 0.74-1.07; P=0.177), he noted.
“Sr89 but not ZA significantly increased bony clinical PFS,” Dr. James concluded. “ZA did, however, significantly increase SRE free interval and decrease total SRE numbers, mostly by effects seen post-progression.”