The use of denosumab (Xgeva) as an alternative to the more commonly prescribed zoledronic acid (Zometa) to slow down the development of bone metastases in men with advanced prostate cancer is becoming more common. The most common concern for men taking Zometa and now Xgeva has been osteonecrosis of the jaw. Osteonecrosis of the jaw is basically severe bone disease which is associated with bisphosphonate therapy (Zometa and now Xgeva).

One of the more common questions asked by many people is if osteonecrosis of the jaw is more or less common in men taking Zometa or Xgeva? The answer is simple; overall 2% of cancer patients treated with denosumab do developed jaw necrosis, which did not significantly different from the 1.45% incidence with Zometa.

According to a retrospective analysis of multiple randomized trials(1) of patients taking Xgeva, patients infrequently developed osteonecrosis of the jaw; however the rate appeared to increase over time in certain subgroups. Specifically, patients with breast and prostate cancers taking Xgeva were twice as likely to develop osteonecrosis of the jaw as treated patients with other solid tumors or multiple myeloma!

Tim van den Wyngaert, MD, of Antwerp University Hospital in Belgium, and colleagues concluded in a poster presentation at the International Conference on Cancer-Induced Bone Disease the longer treatment duration could explain the higher rates in patients with breast and prostate cancer patients. He said, “Current data suggest that additional gains in prevention

[of osteonecrosis of the jaw] are feasible with further education of healthcare providers.” He also said that the findings are hypothesis generating and should be used only to raise awareness, focus on prevention, and guide further research.

An integrated analysis of all three trials showed overall superiority for denosumab (Ann Oncol 2010; 21: Abstract 1249P). Separate analyses demonstrated the superiority of denosumab among patients with breast or prostate cancer and noninferiority versus zoledronic acid in patients with other solid malignancies or myeloma (J Clin Oncol 2011; 28: 5132-5139, Lancet 2011; 377: 813-822, J Clin Oncol 2011; 29: 1125-1132).

Van den Wyngaert noted in the introduction to the data section of the poster that although jaw necrosis is an uncommon complication in cancer, patients who develop it have few effective treatment options, making avoidance a consideration in the use of anti-resorptive agents.

The investigators also concluded that there should be set up “International Prospective ONJ Registries of patients Treated with Bisphosphonates or Denosumab. They should be established to document exposure, risk factors, and treatment in order to increase our understanding of ONJ incidence, biology, and outcome.”

(1)The three large randomized trials of patients treated with either denosumab or zoledronic acid (Bone. 2011;48:S18). The three trials had a similar design and comprised 5,700 patients. The studies involved patients with bone metastases from solid tumors or myeloma and at least one lytic bone lesion. Patients were randomized to denosumab or zoledronic acid, and the primary endpoint was time to a first skeletal-related event (SRE). The three trials showed that patients treated with denosumab and those treated with Zometa had a similar rate of osteonecrosis of the jaw

Primary source: International Conference on Cancer-Induced Bone Disease
Source reference:
Van den Wyngaert T et al. “RANK ligand inhibition in bone metastatic cancer and risk of osteonecrosis of the jaw (ONJ): Updated results with extended phase III data” CIBD 2011; Abstract P106.

Joel T Nowak, M.A., M.S.W.