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Zoledronic acid reduces skeletal complications for men with progressive bony prostate cancer
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The addition of zoledronic acid to docetaxel significantly reduced the rate of skeletal-related events but did not prolong OS or clinical PFS among men with metastatic castrate-refractory prostate cancer, according to results of the TRAPEZE study.
Further, the addition of strontium-89 to docetaxel appeared to improve clinical PFS but had no effect on OS or skeletal-related events, results showed.
Nicholas D. James
The TRAPEZE study — a randomized, open-label, phase 3 trial — sought to assess whether the addition of zoledronic acid, strontium-89, or both to docetaxel would yield clinical benefits for men with bony metastatic castrate-refractory prostate cancer.
However, with the exception of the reduction in skeletal-related events with zoledronic acid and modest clinical PFS benefits of strontium-89, the combinations did not appear to have a great impact on survival.
“At the time of study inception, this [clinical PFS gain], coupled with a modest quality of life gain may have been adequate to change clinical practice,” Nicholas D. James, PhD, FRCR, FRCP, director of University of Warwick Cancer Research Unit in Coventry, U.K., and colleagues wrote. “However we have seen a number of new treatments licensed in the last few years that improve OS postchemotherapy as well as improve quality of life and skeletal-related events. These include abiraterone [Zytiga, Janssen Biotech], enzalatumide [Xtandi, Astellas], cabazitaxel and, of particular relevance to this study, radium-223.”
The investigators enrolled 757 men (median age, 68 years; range, 63-73 years) with metastatic, castrate-refractory prostate cancer between February 2005 and February 2012 and randomly assigned them to one of four treatment arms:
Docetaxel alone;
Docetaxel plus zoledronic acid;
Docetaxel plus strontium-89; or
Docetaxel plus zoledronic acid and strontium-89.
Overall, 46% of the patients completed their docetaxel treatment. Those who did not complete their treatment progressed (29%), experienced intolerable toxic effects (12%) or developed a comorbidity that called for the discontinuation of docetaxel (30%).
Median follow-up was 22 months.
Results of an adjusted Cox regression analysis showed the addition of zoledronic acid had no impact on clinical PFS (HR = 0.98; 95% CI, 0.85-1.14), whereas strontium-89 had a modest effect (HR = 0.85; 95% CI, 0.73-0.99).
OS did not appear improved with strontium-89 (HR = 0.92; 95% CI, 0.79-1.08) or zoledronic acid (HR = 0.99; 95% CI, 0.84-1.16).
However, zoledronic acid significantly prolonged skeletal-related event-free survival (HR = 0.78; 95% CI, 0.65-0.95). Researchers observed a 30% decrease in overall skeletal-related events among patients who received zoledronic acid (425 vs. 605), which may indicate a role for zoledronic acid as postchemotherapy maintenance therapy.
“The prevention of serious events such as fracture, surgery and spinal cord compression is a high priority for clinical services with great pressures on inpatient beds,” James and colleagues wrote. “Hence, a predictable outpatient therapy may be attractive to health care providers if it prevents emergency, unpredictable resource-intense visits.
“It is likely that patients would prefer a preventative treatment such as zoledronic acid to a reactive approach,” they added. – by Anthony SanFilippo
Disclosure: The study was funded in part by Sanofi-Aventis, Novartis and GE Healthcare. James reports consultant/advisory roles with Affinity, Amgen, Astellas, Bayer, Janssen, Novartis and Sanofi-Aventis. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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