狄诺塞麦的疗效好吗？

(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. China announced on May 27 that denosumab (desosumab) has been approved by the National Medical Products Administration for the treatment of giant cell tumors of bone that are unresectable or that may result in severe functional disability after surgical resection, including adults and adolescent patients with skeletal maturity (defined as at least 1 mature long bone and weight ≥45 kg).

Is denosumab effective?

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 the 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 related to 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 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 pointed out that the adverse events of denosumab were 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, denosumab can be used as a new treatment option for patients with giant cell tumor of bone.