2010 Study Shows Denosumab is Superior to
A study released at the 2010 American Society of Clinical Oncologists (ASCO) meeting showed that in men with metastatic prostate cancer Denosumab (Xgeva) demonstrated a longer period before they developed their first skeletal event than those taking zoledronic acid (Zometa)
The study concluded that in men with bone metastasis from castration-resistant prostate cancer (CRPC), a monthly subcutaneous injection with denosumab, 120 mg, is superior to the standard 4 mg of Zometa.
This phase III study which enrolled 1,901 men, who were randomized (1:1), it was double blind, and double-dummy design.
Before randomization, the men were stratified by serum PSA, previous or ongoing chemotherapy, and a prior history of skeletal events (SRE). All of the subjects in the study also received calcium and vitamin D supplementation.
During the study, more than 20% of zoledronic acid men required dose adjustment at baseline because of reduced creatinine clearance levels, while an additional 15% required some dose(s) withheld during the study because of an increase in serum creatinine.
Denosumab achieved the primary endpoint of the study (p=.0002), which was designed to establish its non-inferiority compared with zoledronic acid in the time to first on-study SRE. As a result of this achievement, the researchers also evaluated the secondary efficacy endpoints that investigated the potential superiority of denosumab in extending the time to first and multiple SREs. They found that:
1- Compared with zoledronic acid, denosumab significantly increased the median time to first SRE (20.7 months vs. 17.1 months; 18% risk reduction, p=.008) and had a similar benefit in the multiple event analysis.
2- They found that there were no significant differences between the treatment arms in median PSA over time, overall disease progression, or overall survival.
3 -The researchers found that both treatments were well tolerated, and rates of adverse event-related withdrawals were similar in the two groups (~16%). However, they did find that some differences in safety profiles of the two drugs emerged. They found that acute reactions were more common in men who took zoledronic acid than with denosumab (18.8% vs. 8.4%). On the other hand, men treated with denosumab had higher rates of hypocalcemic events (the presence of low serum calcium levels in the blood) (12.8% vs. 5.8%) and osteonecrosis of the jaw ([ONJ] 2.3% vs. 1.3%).
According to the first author Karim Fizazi, MD, Ph.D., head of the department of cancer medicine, Institut Gustave Roussy, Villejuif, France, “To our knowledge, this is one of the largest phase III trials ever reported of patients with bone metastasis from CRPC…. In addition to the superiority denosumab demonstrated against zoledronic acid in preventing/delaying SREs, this novel agent has other advantages, including its easier route of administration, lack of nephrotoxicity that eliminates any need for renal monitoring and renal function-based dose adjustment, and reduced risk of acute phase reactions."
Presented at the ASCO Meeting – 2010 in Chicago
Joel T. Nowak, MA, MSW wrote this Post. Joel is the CEO/Executive Director of Cancer ABCs. He is a Cancer Thriver diagnosed with 5 primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma and a rare cancer, Appendiceal Cancer.