Although an FDA Reproductive Health Drugs Advisory Committee recommended in August against approving Amgen’s denosumab (Prolia) as a treatment to reduce bone complications in patients with advanced breast cancer, updated data presented today at ECCO/ESMO might elicit a different opinion from an ODAC panel, if convened.
Although an FDA Reproductive Health Drugs Advisory Committee recommended in August against approving Amgen’s denosumab (Prolia) as a treatment to reduce bone complications in patients with advanced breast cancer, updated data presented today at ECCO/ESMO might elicit a different opinion from an ODAC panel, if convened. Amgen announced that a phase III trial comparing denosumab with zoledronic acid (Zometa) found denosumab to be more effective at preventing skeletal-related events (SREs), such as fractures, in 2046 women with bone metastases resulting from advanced breast cancer.
In this 34-month study, patients were randomized 1:1 to receive 120 mg of denosumab subcutaneously every 4 weeks or 4 mg of intravenously administered zoledronic acid every 4 weeks. Patients in the denosumab arm had an 18% reduced risk of experiencing an initial fracture or requiring radiation or surgery to the bone than patients in the zoledronic acid arm. Denosumab also significantly prolonged the time to subsequent SREs. Women treated with zoledronic acid experienced their first on-study SRE at a median of 26.5 months, whereas this median was not reached in the denosumab arm.
In a press release, Alison Stopeck, MD, associate professor of medicine at the Arizona Cancer Center, University of Arizona Health Sciences Center in Tuscon, said, “Denosumab was superior to Zometa in preventing SREs and delayed worsening of bone pain.” She noted that as many as 80% of patients with advanced brain cancer develop bone metastases, which often lead to excruciatingly painful bone complications.
The rates of overall and serious adverse events were similar between the two treatment arms and consistent with those observed in previous studies. Renal toxicity, however, was less common in patients who received denosumab, at 4.9% compared with 8.5% for patients who received zoledronic acid. The rate of osteonecrosis of the jaw was not statistically different between the two groups, with 20 cases occurring in the denosumab arm compared with 14 in the zoledronic acid arm. Overall survival and progression-free survival outcomes were also similar with both treatments. The results of this study make it more likely that an ODAC panel will support approval of denosumab for this indication. The previous review already recommended the drug be approved for men with advanced prostate cancer and patients with osteoporosis. ECCO/ESMO Abstract 2LBA.
In addition to the breast cancer study, results were presented from another phase III trial, which compared denosumab with zoledronic acid in 1776 patients with advanced solid tumors (excluding breast and prostate cancer) or multiple myeloma and bone metastases. The dosages were the same as those used in the breast cancer trial.
While denosumab did not demonstrate superior efficacy to zoledronic acid in this patient population, results were significant for demonstrating denosumab’s no inferiority to zoledronic acid. Patients treated with denosumab experienced their first “on-study” SRE at a median of 20.6 months compared with 16.3 months for those who received zoledronic acid (HR, 0.84; CI, 0.71-0.98).
As with the breast cancer study, patients in both arms had similar rates of adverse effects, including osteonecrosis of the jaw and infections; and overall survival and time to progression were also comparable. Commenting on the study, David Henry, MD, clinical professor of medicine, Pennsylvania Hospital in Philadelphia, said, “It is encouraging to see denosumab’s efficacy in this broad cancer population. There is no need for renal monitoring or dose adjustments due to renal impairment.” The results are more good news for Amgen, which is also reporting positive results from trials involving panitumumab (Vectibix) this week. ECCO/ESMO Abstract 20LBA.