JMT103 versus Non-Denosumab or Denosumab Treatment in Chinese Patients with Unresectable or Surgically Challenging Giant Cell Tumor of Bone: A Propensity Score-Matched Comparison

Abstract

Background: Giant cell tumors of bone (GCTB) are RANK/RANK-ligand positive, progressive osteolytic tumors. There was no medical treatment for GCTB based on efficacy and safety data from Chinese patients. A single-arm, phase II study demonstrated the promising efficacy of JMT103 in unresectable or surgically challenging GCTB. Patient-level outcomes from the single-arm trial were compared with real-world data from denosumab or non-denosumab treated patients to estimate comparative efficacy in unresectable or surgically challenging GCTB.

Methods: The real-world data were retrospectively collected from three hospitals between January 2013 and December 2023. The eligibility criteria of the two cohorts were based on the JMT103 single-arm study. Propensity score matching was used to balance the baseline characteristics of patients in the JMT103 and the real-world cohorts. The primary endpoint was histopathological or 12 week radiological objective tumor response rate (OTR). Secondary endpoints included tumor response rate throughout the study, objective response rate, disease control rate, and safety profiles.

Results: 166 and 135 patients were finally included in the non-denosumab and denosumab cohorts, respectively. After 1:1 nearest neighbor matching, the OTR of the JMT103 cohort was significantly higher than that of the non-denosumab cohort (94.2% vs. 4.8%), and was comparable with that of the denosumab cohort (92.0% vs. 67.0%). The same results were observed in tumor response rate throughout the study (JMT103 vs. non-denosumab: 94.2% vs. 4.8%, JMT103 vs. denosumab: 94.3% vs. 86.4%), objective response rate (83.5% vs. 11.1%, 87.4% vs. 80.0%), and disease control rate (100% vs. 70.4%, 100.0% vs. 98.8%).

Conclusion: JMT103 has manageable safety profiles with better effectiveness than non-denosumab and a trend toward greater effectiveness than denosumab in patients with unresectable or surgically challenging GCTB.

Trial registration: NCT05402865, NCT04255576.

Keywords: JMT103; effectiveness; giant cell tumor of bone; propensity score analysis; safety.

FIGURE 1

Flow diagram chart showing the identification, screening, eligibility and included process of non‐denosumab and denosumab cohorts. A total of 996 patients with GCTB were screened, and ultimately 135 patients treated with denosumab (denosumab cohort) and 166 patients not treated with denosumab (non‐denosumab cohort) were included. *Including malignant transformation of GCTB. GCTB, Giant cell tumor of bone.

FIGURE 2

Standard difference distribution of covariates prior to and after propensity score matching. a. JMT103 vs. non‐denosumab treatment cohort. Standardized differences in most baseline covariates were less than 10% except primary tumor location (11.6%) and relapse (11.3%), indicating a good balance between cohorts. b. JMT103 vs. denosumab treatment cohort. Standardized differences in most baseline covariates were less than 10% except age (11.3%) and relapse (10.2%), indicating a good balance between cohorts. PS, Propensity score; PTL, Primary tumor location; GCTB, Giant cell tumor of bone.

FIGURE 3

Forest plot of subgroup analysis for OTR within 12 weeks. (a) JMT103 vs. non‐denosumab cohort; (b) JMT103 vs. denosumab cohort. All the OTR within 12 weeks of the JMT103 cohort was superior to the non‐denosumab/denosumab cohort in all subgroups (Figure 3a,b).*Resection could not be done without nerve damage or substantial impairment of joint function. N, total number of cases; n, number of response cases. OTR, objective tumor response. OR, odd ratio.