Patients with cancer that has metastasized (spread) may benefit from treatment with Xgeva (denosumab), which has been approved by the FDA (Food and Drug Administration) today. Specifically, Xgeva is designed to protect against skeletal-related events in advanced cancer patients who have bone damage – bone metastasis. Examples of skeletal-related events are bone fractures linked to cancer, and bone pain that requires radiation therapy or surgery.

Human TANKL is a protein involved in the destruction of the bones in patients with cancer. Xgeva, a monoclonal antibody, tagets human RANKL. Zometa (zoledronic acid) and Aredia (pamidronate disodium), two other medications, also have similar indications.

Patients with multiple myeloma or other blood cancers should not be given Xgeva, the FDA informs.

Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said:

    “Bone metastases represent a major cause of pain and suffering in patients with cancer and can affect a patient’s quality of life. Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer.”

Bone metastasis is the spread of cancer to the bones.

Three randomized, double-blind clinical trials involving 5,723 participants which compared Xgeva with Zometa for safety and effectiveness confirmed those primary endpoints – in other words, the drug was found to be safe and effective. One of the studies was with breast cancer patients, another with prostate cancer, and the other involved patients with several different types of cancers.

The studies aimed to measure how long it took for a fracture or cord compression to occur, as well as length of time before radiation or surgery to treat bone pain was required.

Xgeva was found to be better than Zometa in delaying skeletal related events (SREs) in breast and prostate cancer patients. Among the prostate cancer participants on Xgeva, the average time was 21 months, compared to 16 months for those on Zometa.

Breast cancer patients on Zometa have taken an average of 26 to experience an SRE. The length of time for those on Xgeva has not been reached yet, the FDA wrote today.

Among those with other cancers (other solid tumors), there was no significant difference in time to develop an SRE between the two drugs. Most of the patients with other cancers had non-small cell lung cancer, kidney cancer, small cell lung cancer, and multiple myeloma.

The most serious adverse events linked to Xgeva use were hypocalcemia (low calcium blood levels) and osteonecrosis of the jaw.

Denosumab, under the brand name Prolia, was approved in June this year for postmenopausal females who were at higher risk of developing bone fractures. Xgeva is given at a higher dose for cancer patients than Prolia is to post-menopausal women, and also more frequently. Xgeva’s profile for patients with cancer and bone metastases is different from Prolia’s.

Kevin Sharer, chairman and chief executive officer of Amgen, the marketers of Xgeva, said:

    “Today’s approval of XGEVA illustrates what is possible when scientific innovation, commitment and investment come together to advance medicine. A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating. We are pleased to offer this new advance to patients and their healthcare providers.”

David H. Henry, M.D., clinical professor of medicine, and vice chair, Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Healthcare System, said:

    “As many as 3 out of 4 patients with advanced prostate, lung, and breast cancer will experience spread to their bones. Despite the availability of current treatments, a significant proportion of these patients still experience bone complications or are not candidates for existing treatment. Based on the compelling science and robust clinical evidence seen with XGEVA, I expect this new option to quickly become a mainstay of cancer care and to play an important role in reducing the incidence of debilitating bone complications in patients with advanced cancer.”

Bone metastases are estimated to cost the US economy approximately $12 billion each year. Cancer patients who have an SRE linked to bone metastases subsequently incur much higher medical costs, compared to similar patients who don’t. A patient who does have an SRE has a much higher risk of eventually having another one.

Sources: FDA, Amgen

Written by Christian Nordqvist