Denosumab increases bone metastasis-free survival in men with castrate-resistant metastatic prostate cancer

Denosumab (Xgeva, Amgen) significantly increased bone metastasis-free survival for more than 4 months in men with castrate-resistant metastatic prostate cancer that had not yet spread to bone, according to results of a landmark study of Xgeva, presented at a late-breaking plenary session at the American Urological Association’s 2011 annual meeting in Washington, D.C.

Xgeva, a fully human monoclonal antibody that binds to RANK Ligand, was approved in November 2010 for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

The '147 study, a randomized, placebo-controlled, multicenter phase 3 trial, evaluated Xgeva versus placebo in 1,432 men with castrate-resistant prostate cancer. The ‘147 study demonstrated that Xgeva significantly improved median bone metastasis-free survival by 4.2 months (HR=0.85; 95% CI, 0.73–0.98, P=.03) compared to placebo (primary end point), and significantly improved time to first occurrence of bone metastases (secondary end point). Overall survival was similar between the Xgeva and placebo groups (secondary end point).

“The results of the ‘147 study are an important step in trying to modify the course of advanced prostate cancer and the complication of bone metastases,” said Amgen spokesperson Lisa Rooney. “With effective therapies now in place for both early [castrate-sensitive] prostate cancer and advanced [castrate-resistant] prostate cancer, there is a gap in the treatment plan for those patients who are castrate-resistant but have not yet developed metastatic disease. “Prolonging the pre-metastatic phase of castrate-resistant disease addresses an important unmet medical need and helps contribute to making recurrent prostate cancer a chronic disease.”

Two major adverse events that can occur in patients taking Xgeva is severe hypocalcemia and osteonecrosis of the jaw.

Xgeva is the first and only bone-targeted therapy that has shown the ability to prevent the spread of cancer to the bone in a large randomized study, according to Rooney.

“There is a very significant opportunity for denosumab to help manage patients with prostate cancer who experience bone metastases,” said Roy Baynes, MD, vice president, global development, hematology/oncology at Amgen.

Bone is the most common place for prostate cancer to spread; up to 90% of men with prostate cancer will experience bone metastases. Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 75% of patients with metastatic disease. The total economic burden of patients with bone metastases in the United States alone is estimated to be $12.6 billion annually.

Xgeva is administered as a single 120-mg subcutaneous injection every 4 weeks. “It is quicker and infinitely more convenient for the patient than an IV infusion,” said practicing urologist Neal D. Shore, MD, FACS, medical director, Carolina Urologic Research Center, Myrtle Beach, S.C. “It is extremely beneficial in terms of cost.”

Amgen intends to submit its data to FDA in the first half of this year.