1. The change of uNTx/uCr (a marker of bone resorption) was within the equivalence margin in the MW032 group and in the denosumab group across the 53 weeks of follow-up.
2. Treatment-related adverse events grade 3 or worse occurred at similar rates across both groups (53.8% in the MW032 group and 57.6% in the denosumab group).
Evidence Rating Level: 1 (Excellent)
Study Rundown: Metastatic bone disease is a common complication of cancer resulting in skeletal-related events (SREs). Denosumab, a human monoclonal antibody, has shown efficacy in inhibiting osteoclast function and preventing SREs in patients with metastatic bone disease, and MW032, a biosimilar to denosumab, demonstrated bioequivalence in a phase 1 study. This study was a phase 3 equivalence trial that assessed efficacy, safety, and pharmacokinetics in patients with solid tumour bone metastases. The primary endpoint was a change in urinary N-telopeptide/creatinine ratio (uNTx/uCr, a marker of bone resorption), and secondary endpoints included a change in bone-specific alkaline phosphatase (s-BALP, a marker of osteoblast activity), the incidence of SREs, and safety. The change in uNTx/uCr was −1.27 in the MW032 group and −1.30 in the denosumab group, with a difference of 0.02 which was within the equivalence margin, and this translated to a mean percent change of uNTx/uCr from baseline −72.0% and −72.7% respectively. There was no significant difference in the percentage change of uNTx/uCr or s-BALP between the two groups at any time point during the 53 weeks of follow-up. The pharmacokinetic parameters were found to be similar for both groups and within the equivalent interval. The difference in SRE incidence was observed to be −1.4% in favor of MW032, but non-significant, with an odds ratio 0.8, and HR 0.87. With regards to safety, common treatment-related adverse events included hypocalcemia (35.6% in MW032 vs 41.2% in denosumab), hypophosphatemia (15.7% vs 10.7%) and hyperuricemia (6.8% vs 5.9%). Treatment-related adverse events grade 3 or worse occurred in 53.8% of the MW032 group and 57.6% in the denosumab group. Osteonecrosis of the jaw occurred in only 1 patient (MW032 group). The strengths of this study included its sample size and methodology, and the limitations included the length of follow-up and lack of clinical endpoints such as overall survival. Overall, it was found that MW032 had similar efficacy, pharmacokinetics, and safety to denosumab in patients with solid tumors and bone metastases.
Click to read the study in JAMA Oncology
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In-Depth [randomized controlled trial]: This double-blind multicenter phase 3 trial enrolled adults with histologically confirmed solid malignancy with radiographic evidence of at least 1 bone metastasis and randomized them (1:1) to MW032 (n=354) or denosumab (n=354). Breast cancer was the primary tumor in almost half of the patients and SREs occurred before baseline in most patients. The change in uNTx/uCr was −1.27 in the MW032 group and −1.30 in the denosumab group, with a difference of 0.02 (90%CI, -0.04-0.09) which was within the equivalence margin (−0.13 to 0.13). This translated to a mean percent change of uNTx/uCr from baseline −72.0% and −72.7% respectively. There was no significant difference in the percentage change of uNTx/uCr or s-BALP between the two groups at any time point during the 53 weeks of follow-up. The pharmacokinetic parameters were found to be similar for both groups and within the equivalent interval. The difference of SRE incidence was observed to be −1.4% in favor of MW032, but non-significant (95%CI, −5.8%-3.0%), with odds ratio 0.8 (95%CI, 0.6-1.1), and HR 0.87 (95%CI, 0.54-1.39). With regards to safety, common treatment-related adverse events included hypocalcemia (35.6% in MW032 vs 41.2% in denosumab), hypophosphatemia (15.7% vs 10.7%) and hyperuricemia (6.8% vs 5.9%). Treatment-related adverse events grade 3 or worse occurred in 53.8% of the MW032 group and 57.6% in the denosumab group. Osteonecrosis of the jaw occurred in only 1 patient (MW032 group). Overall, it was found that MW032 had similar efficacy, pharmacokinetics, and safety to denosumab in patients with solid tumors and bone metastases.
Image: PD
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