地舒单抗治疗效果如何？

It is a monoclonal antibody that binds to RANKL, a protein essential for maintaining bone health. RANKL is also present in giant cell tumors of bone. Desosumab is used in patients whose giant cell tumor of bone cannot be removed by surgery (unresectable) or where surgery would cause serious morbidity (such as amputation or joint removal). Only skeletally mature adolescent patients should use this drug.

How effective is denosumab treatment?

Sant Chawla et al. of Sarcoma Cancer Center in the United States designed a phase 2 clinical study to determine the effectiveness and safety of denosumab in patients with giant cell tumor of bone.

This study is an international multi-center, open-label, parallel-group phase 2 clinical study. All subjects included in the study were histologically identified as giant cell tumors of bone. These patients all had active lesions as assessed by imaging studies. The inclusion criteria for subjects are adults or adolescents who are skeletally mature (with imaging evidence to support the maturity of at least one long bone), are at least 12 years old and above, and weigh at least 45kg.

The researchers divided subjects who met the above criteria into three cohorts. Cohort 1 was patients with giant cell tumor of bone who were inoperable, cohort 2 was patients with giant cell tumor of bone who were operable but had severe surgical complications, and cohort 3 was patients with giant cell tumor of bone from previous clinical studies of denosumab.

Subjects in Cohorts 1 and 2 received a treatment regimen of 120 mg denosumab subcutaneously every 4 weeks. The dose was increased to the loading dose on days 8 and 15 of the first course of treatment, and subjects in Cohort 3 continued the Xgeva denosumab treatment regimen in the previous study.

Investigators assessed patients' disease status and clinical benefit every 4 weeks. The primary endpoint of the study was the safety of denosumab treatment (mainly evaluated through adverse events and abnormal laboratory test results).

Secondary endpoints were the time to disease progression for subjects in cohort 1 and the proportion of subjects in cohort 2 who had not received surgical treatment at 6 months. Safety and efficacy evaluations included all subjects who received at least one dose of denosumab.

Between September 9, 2008, and March 25, 2011, the researchers enrolled a total of 282 subjects, including 10 adolescents. Among them, the data of 281 people were included in the final safety evaluation, 3 people (1%) developed osteonecrosis of the jaw, and 15 people (5%) developed hypocalcemia. The most common grade 3-4 adverse events were as follows: hypophosphatemia in 9 people (3%), anemia in 3 people (1%), back pain in 3 people (1%), and extremity pain in 3 people (1%).

Serious adverse reactions occurred in 25 patients (9%) and there were no treatment-related deaths. Based on the investigator's assessment of the subject's disease status, after 13 months of follow-up, 163 (69%) of the 169 evaluable subjects in Cohort 1 had not experienced disease progression.

Of the 100 evaluable subjects in Cohort 2, 74 (74%) did not undergo surgery, and of the 26 subjects (62%) who did, 16 (62%) had fewer complications than expected. The median follow-up time for cohort 2 was 9.2 months.

The study results indicate that the adverse events of denosumab are consistent with the known safety profile. In patients with giant cell tumor of bone, denosumab can increase tumor response to treatment and reduce complications from surgical treatment. Therefore, it can be used as a new treatment option for patients with giant cell tumor of bone.