地诺单抗治疗骨转移效果

On November 18, 2010, the FDA approved the indication for denosumab for the treatment of bone metastases from solid tumors. This indication was based on the results of a total of three published phase III pivotal clinical trials compared with zoledronic acid.

These three randomized, double-blind trials included a total of 5723 cancer patients: Trial 1 was breast cancer patients with bone metastases; Trial 2 was prostate cancer patients with bone metastases; Trial 3 was solid tumors other than breast and prostate cancer with bone metastases and multiple myeloma. The efficacy of denosumab and zoledronic acid (a bisphosphonate) was compared in the treatment of bone metastases in breast cancer, prostate cancer and other solid tumors, as well as in multiple myeloma.

Comprehensive analysis of these three studies showed that compared with zoledronic acid: denosumab prolonged the time to the patient's first adverse bone event (ARE) by 17%, or significantly delayed the median time to the first SRE by 8.2 months (27.6 months vs. 19.4 months for zoledronic acid); denosumab prolonged the time from the first to the recurrence of SRE in the study by 18%. Denosumab also significantly prolonged the time to worsening pain compared with zoledronic acid in patients with mild or no pain at study entry. Based on this, denosumab is also recommended in NCCN guidelines for patients with bone metastases from solid tumors.

The 2016 American Congress of Clinical Oncology (ASCO) was held in Chicago. As one of the most watched academic conferences in the field of oncology, the new research and new progress published at each ASCO conference are the focus of everyone's attention. Among these hot spots of much attention, there is no shortage of Chinese research. A "head-to-head" randomized double-blind phase III clinical study conducted by Professor Jiang Zefei, Director of the Breast Cancer Department of the Affiliated Hospital of the Academy of Military Medical Sciences (Beijing 307 Hospital) and others showed that denosumab is significantly more effective than zoledronic acid in Asian patients with bone metastasis from solid tumors. This study included a total of 485 adult patients (ECOG score 0-2) who had been diagnosed with bone metastases from solid tumors (mainly breast cancer and non-small cell lung cancer). They were randomly divided into the denosumab group (n = 326, 120 mg, subcutaneous injection, once every 4 weeks) and the zoledronic acid group (n = 159, 4 mg, intravenous injection, once every 4 weeks) in a 2:1 ratio. They were treated for 49 weeks and followed up until 73 weeks. The primary endpoint was the percent change from baseline in urinary creatinine-adjusted urinary type I collagen cross-linked amino terminal peptide (uNTx/uCr) at 13 weeks, with additional endpoints being the change from baseline in bone-specific alkaline phosphatase (S-BALP) at 13 weeks and time to first bone-related event during the study period.

The results showed that the change in uNTx/uCr was -81.9% in the denosumab group and -75.2% in the zoledronic acid group. There was a significant difference between the two groups. The mean change in S-BALP from baseline was -36.8% in the denosumab group and -30.3% in the zoledronic acid group, with a significant difference between the two groups. The proportion of patients who experienced bone-related events in the first year of the study period was lower in the denosumab group than in the zoledronic acid group. There was no significant difference in the incidence of adverse events between the two groups.

It is not difficult to see from the above research results that denosumab is more effective than zoledronic acid in preventing bone-related events after bone metastasis from solid tumors, and there is no risk of safety. The trial again demonstrated superiority to zoledronic acid in bone metastases from solid tumors.