Xgeva治疗骨转移效果如何？

Denosumab is a RANKL inhibitor, clinically used to treat unresectable giant cell tumors of bone in adults and skeletally mature adolescents; hypercalcemia caused by malignant tumors; increasing bone mass in patients with high risk of fractures, including androgen castration therapy for non-metastatic prostate cancer or adjuvant therapy with aromatase inhibitors for breast cancer; preventing bone-related events in patients with bone metastases from solid tumors; and treating osteoporosis in postmenopausal women with a high risk of fractures, but not in patients with multiple myeloma or other leukemias.

How effective is Xgeva denosumab in treating bone metastasis?

For solid tumor bone metastasis, Xgeva denosumab's safety and efficacy data come from three global randomized, double-blind controlled trials. In the three trials, patients were randomly assigned to denosumab (120 mg every four weeks) or zoledronate (4 mg every four weeks). Patients with creatinine clearance less than 30 mL/min were excluded. The primary endpoint of the trial was time to first bone-related events (SREs) that was non-inferior to zoledronic acid.

Study 20050136 (NCT00321464) included 2046 patients with advanced breast cancer with bone metastases. Forty percent of patients had experienced bone-related events, 40% had received chemotherapy within 6 weeks before randomization, 5% had received oral bisphosphonates, and 7% were from Japan. The median age of all patients was 57 years, 80% of patients were white, and 99% were female.

Study 20050244 (NCT00330759) enrolled 1,776 adults with bone metastases from solid tumors (excluding breast cancer, prostate cancer, multiple myeloma, etc.). At the time of randomization, 87% of patients were receiving systemic anticancer therapy, 52% had experienced a bone-related event, 64% were male, 87% were white, and the median age was 60 years. Among all patients, 40% had non-small cell lung cancer, 10% had multiple myeloma, 9% had renal cell carcinoma, and 6% had small cell lung cancer. Other types of tumors each account for no less than 5% of the enrolled population.

Study 20050103 (NCT00321620) included 1901 men with castration-resistant prostate cancer with bone metastases. 26% of patients had previous bone-related events, 15% had a PSA less than 10 ng/mL, and 14% had received chemotherapy within 6 weeks before randomization. The median age of all patients was 71 years, and 86% of patients were white.

The results of the above three trials showed that compared with zoledronic acid, denosumab effectively delayed the occurrence of the first bone-related event.

Lung cancer and other solid tumors (including multiple myeloma): Xgeva denosumab: 20.5 months vs. zoledronic acid: 16.3 months.

Lung cancer and other solid tumors (excluding multiple myeloma): Xgeva denosumab: 21.4 months vs. zoledronic acid: 15.4 months.

Prostate cancer bone metastasis: Xgeva denosumab: 20.7 months vs. zoledronic acid: 17.1 months.

Breast cancer bone metastases: 60% of patients in the Xgeva denosumab group had no serious bone-related events within 27 months (end of trial) vs. more than 50% of patients in the zoledronic acid group had serious bone-related events before the end of the trial.

Overall, the effect of treating bone metastases is very good.