The FDA has approved Xgeva (denosumab), an osteoporosis drug reformulated to reduce the risk of bone fractures and bone pain in patients with cancer that has spread throughout the body.
The FDA based its approval on three clinical trials involving more than 5,700 patients with various cancers, including breast and prostate cancer. The trials compared Xgeva with a similar drug, Zometa.
Researchers looked at groups of cancer patients on one of the two medications and measured the time until occurrence of skeletal-related events such as a bone fracture or spinal cord compression due to their cancer or until surgery or radiation was needed to alleviate severe bone pain.
The clinical trial results showed Xgeva was more effective overall than Zometa in preventing skeletal-related events; among men with prostate cancer, the median time to developing a bone fracture or cancer-related bone pain requiring treatment was 21 months among those taking Zometa vs. 17 months for those taking Xgeva.
Likewise, among women with breast cancer, the median time was 26 months for patients taking Zometa, whereas cancer-related bone injuries had not yet occurred among those taking Xgeva during the study period.
Among patients with solid tumors, including patients with non-small-cell lung cancer, kidney cancer, and small-cell lung cancer, the time to developing cancer-related bone injuries or pain was the same between those taking Zometa and those taking Xgeva.
Xgeva has not been approved by the FDA for patients with multiple myeloma or other cancers of the blood.
"Bone metastases represent a major cause of pain and suffering in patients with cancer and can affect a patient's quality of life," said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research. "Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer."
A Costly Problem
Cancer-related bone injury and pain is common in advanced cancer. According to Amgen, the California-based biotechnology company that manufacturers Xgeva, as many as 75% of patients with advanced lung, prostate, or breast cancer experience cancer spreading to their bones, known as metastases. Amgen reports that the total economic burden of patients with bone metastases in the U.S. is about $12.6 billion annually."A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating," says Kevin Sharer, Amgen's chairman and chief executive officer, in a news release. "We are pleased to offer this new advance to patients and their health-care providers."
There were some side effects from Xgeva, including low calcium levels in the blood and osteonecrosis of the jaw, a severe disease in which the jawbone does not receive enough blood flow and an area of jawbone dies.
Xgeva works by targeting a protein involved in cancer-related bone deterioration called human RANKL. The drug was already approved in June under the brand name Prolia for the treatment of women with postmenopausal osteoporosis who are at high risk of bone fracture. Cancer patients on Xgeva will receive higher doses and more frequent treatments than patients taking Prolia.
