地诺单抗治疗骨转移治疗效果如何？

(Denosumab) is a human immunoglobulin G2 (IgG2) monoclonal antibody with high specificity and affinity for RANKL. RANK receptor signaling promotes osteolysis and tumor growth. Desosumab inhibits tumor growth and reduces bone destruction by binding to RANKL and preventing it from activating RANK on the surface of osteoclasts, osteoclast precursors and osteoclast-like giant cells. The FDA approved this product for use in postmenopausal women with osteoporosis who are at high risk of fracture. It can help reduce the incidence of vertebral, non-vertebral and hip fractures in postmenopausal women with osteoporosis. This product is also used in patients for whom other current treatments are ineffective or intolerable to reduce the risk of fractures.

A 3-year randomized, double-blind, placebo-controlled phase III clinical trial FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) evaluated the efficacy and safety of denosumab in the treatment of osteoporosis in postmenopausal women. Patients were randomized to treatment (denosumab 60 mg subcutaneously every 6 months, n = 3902) or placebo (n = 3906). The primary outcome measure was the incidence of new vertebral fractures over the 3-year period, and secondary outcomes included the incidence of hip and nonvertebral fractures and the time to first fracture during the observation period. The subjects were aged between 60 and 90 years old, with an average age of 72.3 years. The basic T-score value of the spine or total hip was between -4.0 and -2.5 (the average was -2.8). About 23% of the subjects had a history of at least one fracture before entering this trial. All patients also received daily supplements of 1,000 mg of vegetarian calcium and 400 to 800 IU of vitamin D. The results showed that compared with the placebo group, the incidence of new vertebral fractures in the treatment group was reduced by 68% (2.3% in the treatment group and 7.2% in the placebo group, P < 0.000 1), the incidence of hip fractures was relatively reduced by 40% (0.7% in the treatment group and 1.2% in the placebo group, P = 0.036), and the incidence of non-vertebral fractures was relatively reduced by 20%. (6.5% in the treatment group and 8.0% in the placebo group, P =0.011).

Another randomized, placebo-controlled phase III clinical trial, DEFEND (Denosumab Fortifies Bone Density), evaluated the role of denosumab in preventing osteoporosis in postmenopausal women. The average age of the subjects was 59.4 years old, and the spine T-scores were between -1.0 and -2.5 (the average was -1.61). They were randomly divided into a treatment group (denosumab 60 mg subcutaneous injection, once every 6 months, n = 166) or a placebo group (n = 166). All patients were supplemented with $1,000 of vegetarian calcium every day. mg, and the need for vitamin D supplementation is determined by the subject's plasma 25-hydroxyvitamin D level. The main evaluation index is the change in spinal BMD measured by dual energy X-ray absorptiometry (DXA) compared with the baseline level. The results showed that after 24 months, denosumab significantly increased the BMD value of the spine compared with placebo (an increase of 6.5% in the treatment group and a decrease of 0.6% in the placebo group). In addition, the BMD values ​​of all tested sites, including the hip and distal radius, increased significantly in the treatment group. At the same time, markers of bone resorption and formation were significantly reduced. The overall incidence of adverse reactions in the treatment group was similar to that in the placebo group during the observation period. This shows that the therapeutic effect on bone metastases is still good.