The US Food and Drug Administration this week approved denosumab (XGEVA, Amgen) for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. Also this week, approval was granted for eribulin mesylate injection (Halaven, Eisai) for treatment of metastatic breast cancer.
Denosumab
Denosumab is the first bone-targeted therapy for cancer patients to be approved by the FDA in nearly a decade. Approval was granted following a 6-month priority review. The approval was based on results of three phase 3 trials that compared denosumab given every 4 weeks as a subcutaneous injection with zoledronic acid (Zometa, Novartis) delivered every 4 weeks via intravenous infusion. The clinical program included more than 5700 patients with more than 50 tumor types. In patients with breast or prostate cancer and bone metastases, denosumab was shown to be superior to zoledronic acid in reducing the risk of SREs. In patients with bone metastases due to other solid tumors or bone lesions due to multiple myeloma, denosumab was found to be noninferior to zoledronic acid in reducing the risk of an SRE.
Denosumab is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function, and survival of osteoclasts (the cells that break down bone). By preventing RANK Ligand from activating its receptor RANK on the surface of osteoclasts, the drug reduces bone destruction.
Denosumab is not indicated for prevention of SREs in patients with multiple myeloma.
Eribulin
Eribulin mesylate was approved to treat patients with metastatic breast cancer who have received at least two previous chemotherapy regimens for late-stage disease. Prior therapy should have included an anthrcycline and a taxane.
Approval was based on a phase 3 study of 762 patients with metastatic breast cance who were randomized to either treatment with eribulin or another single-agent therapy chosen by their oncologist. Median overall survival was 13.1 months for patients receiving eribulin compared with 10.6 months for controls.
Eribulin, a synthetic form of a chemotherapeutically active compound derived from sea sponge, is a microtubule inhibitor believed to inhibit cancer cell growth.
Side effects reported include neutropenia, anemia, leukopenia, alopecia, fatigue, nausea, asthenia, peripheral neuropathy, and constipation.