A new drug called denosumab may soon give Zometa (zoledronic acid) competition as the standard of care in treating bone metastases in patients with advanced breast cancer. Patients taking denosumab not only had fewer bone complications, but they took longer to develop compared with Zometa, reported researchers of a phase 3 study presented Thursday at the San Antonio Breast Cancer Symposium.
For the 2,046 patients given either denosumab or Zometa, denosumab reduced the risk of developing a single skeletal-related event (fracture, radiation, or surgery to the bone, or spinal cord compression) by 18 percent compared with Zometa. For patients who developed multiple skeletal-related events, denosumab reduced the risk by 23 percent. In total, there were 474 skeletal-related events in 30.7 percent of patients in the denosumab group versus 608 events in 36.5 percent of patients on Zometa.
Plus, denosumab better controlled bone pain, with a median of 88 days until patients experienced moderate or severe pain, compared with 64 days with Zometa.
Both drugs were given every four weeks, and patients were encouraged to take calcium and vitamin D supplements each day.
Side effects, such as short-term flu-like symptoms, were similar between the two arms, but Zometa caused more side effects overall. The only exception was hypocalcemia (a low level of calcium in the blood), which was more common in the denosumab group. A small percentage of patients in both arms experienced severe jaw damage, known as osteonecrosis of the jaw (2 percent with denosumab and 1.4 percent with Zometa), and kidney problems (4.9 percent and 8.5 percent, respectively). Lead study investigator Alison Stopeck, MD, of the University of Arizona Cancer Center, told reporters that these findings show that osteonecrosis of the jaw is not a class effect of bisphosphonates (like Zometa), but rather an effect of all drugs that inhibit osteoclasts, the cells that break down bone.
Denosumab, a monoclonal antibody, is given as a subcutaneous injection and works by blocking a protein called RANK ligand, which tells the body to remove bone. Zometa, an intravenous bisphosphonate, uses a slightly different strategy—it attaches directly to the surface of bone to halt bone breakdown.
Amgen, the maker of denosumab, plans to file the drug for approval in the first quarter of next year for the treatment of bone metastases, said Lisa Rooney, a spokesperson for the company. In addition to the study presented at the meeting, research demonstrating denosumab’s effectiveness in prostate cancer and other solid tumors will be part of the approval application, she said.
This article is a part of CURE’s 2009 San Antonio Breast Cancer Symposium coverage. To read more articles from SABCS 2009, visit sabcs2009.curetoday.com.
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