Last Updated: 2010-12-10 16:32:05 -0400 (Reuters Health)
By Bill Berkrot
NEW YORK (Reuters) - Amgen Inc's new osteoporosis drug denosumab delayed fractures and other bone problems in patients with advanced breast cancer five months longer than Novartis AG's Zometa, according to data from a large clinical trial.
The data were longer term follow-up results from a study in which the Amgen drug proved better by 18 percent at delaying the time for first fracture or other skeletal-related event and 22 percent better in time to first and subsequent event in women whose breast cancer had spread to the bone.
Denosumab last month won U.S. approval to be sold under the brand name Xgeva for reducing the risk of skeletal-related events in patients whose solid tumor cancers had spread to the bone. It is sold under the name Prolia as a treatment for osteoporosis.
In this extension of the previously reported study, patients on the Amgen drug on average went 32.4 months before experiencing a first skeletal related event. That compared with 27.4 months for those who received Zometa, which is known chemically as zoledronic acid.
"The findings confirm what we saw in the primary analysis. Xgeva continues to be superior in terms of efficacy," Roy Baynes, Amgen's vice president of global development and therapeutic head of hematology and oncology, said in a telephone interview.
"They reinforce the efficacy; they reinforce the superiority and they continue to show a very similar safety profile" to Zometa, said Baynes, adding that the Novartis drug had been considered the gold standard of care.
Skeletal-related events in the trial were defined as fractures, need for radiation or surgery to the bone or spinal cord compression.
"The average life expectancy of patients with metastatic breast cancer is approximately 2.5 years, so if you can prolong the time without a skeletal-related event by five months you are substantially benefiting the patient," Dr Alison Stopeck, the study's lead investigator who presented the data at the San Antonio Breast Cancer Symposium on Friday, said in a statement.
Overall survival and disease progression was similar in patients in both treatment groups.
Subjects in the 2,046-patient study received either a 120-milligram injection of denosumab or a 4 mg intravenous infusion of Zometa every four weeks. Both drugs, while from different classes of medicines, work by inhibiting the cells that break down bone cells called osteoclasts.
Once the study's full results became available and the Amgen drug was confirmed as clearly superior, Zometa patients in the trial were switched over to Xgeva, Amgen said.
The rate of side effects was 96.2 percent for denosumab patients and 97.4 percent for those on Zometa, which is not unusual for advanced cancer patients on chemotherapy and other medicines, such as hormone treatments.
There was a slightly higher incidence of osteonecrosis of the jaw with denosumab patients - 2.5 percent versus 1.8 percent on Zometa - but the difference was deemed to be not statistically significant.
Osteonecrosis of the jaw is a potentially serious side effect in which the jaw bone essentially dies due to lack of blood flow. But about 40 percent of the patients with osteonecrosis improved.
"For the most part it was manageable and tolerable," Baynes said.
Denosumab, or Xgeva, has other advantages in addition to the more convenient method of administration. It does not cause the flu-like symptoms sometimes associated with the Novartis drug and it does not need to be dosed according to a patient's kidney function as Zometa does.
"We now have an alternative to zoledronic acid that is more convenient, less toxic and more effective for patients with bone metastases," Stopeck said.
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