US Food and Drug Administration (FDA) experts have decided against expanding denosumab’s indications to include prophylaxis against bone metastasis in high-risk castrationresistant prostate cancer. Marketed as Xgeva by Amgen, denosumab inhibits bone loss and fractures, and is already approved for patients with metastatic bone tumours. Amgen’s phase 3 clinical trial of denosumab administration before bone metastasis in patients with castration-resistant prostate cancer found denosumab slowed metastasis to bone. But early denosumab administration did not improve survival rates, and had a signifi cant 5% risk of osteonecrosis of the jaw. That troubled members of the FDA Oncologic Drugs Advisory Committee, who voted 12 to 1 against recommending the agency approve the expanded indication, noting that without clear evidence of clinical benefi ts, denosumab administration before metastasis only imposes on patients “the increased risks of the drug”. What bone-metastasis-free survival— Amgen’s primary endpoint, based on bone imaging—really means for patient survival or quality of life is unclear, the panel decided. “Unfortunately, there wasn’t an endpoint directly measuring clinical benefi ts like symptomatic bone metastasis or skeletal events”, Brent Logan (Medical College of Wisconsin, Milwaukee, WI, USA) told The Lancet Oncology. A few patients might benefi t from early treatment, but most wouldn’t— and many would have osteonecrosis, cautioned Maha Hussain (University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA). “The rate of osteonecrosis is likely to go higher the longer you treat patients”, said David Quinn (Norris Comprehensive Cancer Centre, University of Southern California, CA, USA). “This was a relatively early snapshot of these patients. There’s a concern that these patients are likely to be living longer, thanks to the other drugs we’ve got—and that we’ll see a major issue with osteonecrosis or other unanticipated side eff ects.” Agents to prevent metastasis in these patients are not available, Hussain said. “But there has to be good reason to treat”, Hussain said. “Unmet need does not justify suboptimal treatment. We need to go back to the drawing board and look at agents and endpoints, and whether we should be adding more drugs.”