Second of Three Pivotal Phase Three Bone Metastases Trials Meets Primary Endpoint Denosumab Delayed Time to Skeletal Related Events
Amgen (NASDAQ: AMGN) has announced positive results from a Phase III head-to-head trial evaluating denosumab administered subcutaneously, versus Zometa (zoledronic acid) administered as an intravenous (IV) infusion. Currently Zometa is the FDA approved treatment for bone metastases and bone density problem
The primary endpoint of this study which was achieved was that patients treated with denosumab experienced a similar time to first skeletal-related event (SRE) (fracture, radiation to bone, surgery to bone, or spinal cord compression) compared with those receiving Zometa (hazard ratio 0.84, 95 percent CI: 0.71-0.98), which is statistically significant. Although numerically greater, the delay in the time to first SRE associated with denosumab treatment was not statistically superior compared to Zometa (adjusted p=0.06) (secondary endpoint). The time to first-and-subsequent SRE was also numerically greater but not statistically superior compared to Zometa (hazard ratio 0.90, 95 percent CI: 0.77-1.04) (secondary endpoint). What this means is that denosumab seems to be equally effect as Zometa.
The incidence of adverse events and serious adverse events was consistent with what has previously been reported for these two agents. Rates of osteonecrosis of the jaw (ONJ) were balanced and infrequent in both treatment groups (10 patients receiving denosumab as compared with 11 patients receiving Zometa). Infectious adverse events were balanced between the two treatment arms, as was overall survival and the time to cancer progression.
“We are extremely pleased with these results, which continue to demonstrate that inhibiting RANK Ligand with denosumab provides a clinically meaningful benefit for advanced cancer patients with solid tumors that have metastasized to the bone, and to patients with multiple myeloma, both groups who routinely suffer SREs,” said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. “We are very encouraged by the overall strength of the data, which we will present in a scientific forum later this year. We are also looking forward to reviewing the results of a final SRE study, in patients with advanced prostate cancer, next year.”
Bone metastases, the spread of tumors to the bone, are a serious concern for many advanced cancer patients, including men suffering from prostate cancer. When cancer spreads to the bone, the growing cancer cells weaken and destroy the bone around the tumor. This damage can result in a number of serious bone complications, collectively called SREs.
Even though denosumab did not prove better than Zometa, having an alternate drug will be beneficial. Now we wait for the company to put the results of the three trials that it has run into a package and presents it to the FDA. Denosumab, a drug that is on the horizon for the treatment of advanced prostate cancer.
Joel T Nowak MA, MSW