Giant cell tumor of bone: Effect of longer dosing intervals of denosumab on tumor control and bone related complications.

Abstract

11525 Background: Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone neoplasm characterized by osteoclast activation causing destructive osteolysis. Denosumab, a human monoclonal antibody against RANK ligand, has emerged as an effective treatment option when surgery is not recommended, but can cause significant bone toxicity. Current standard dosing is every 4 weeks after 3 weekly loading doses. As patients (pts) with GCTB are often young adults, frequent denosumab administration long-term may be burdensome and associated with increased risk of complications. We assessed whether alternative, longer dosing intervals are associated with differences in efficacy or bone toxicity. Methods: Retrospective chart review was conducted on GCTB pts over 18 years old at University of Michigan who received at least 1 year of standard denosumab treatment. Pts were identified using a free-text medical record search engine with keywords “giant cell tumor” and “denosumab” until August 2020. We compared bone-related adverse effects and tumor control in pts who continued denosumab every 4 weeks versus longer treatment intervals. Decision to increase interval between doses was based on provider and pt discussion and preference as part of routine medical care. Results: 37 GCTB pts were identified; 51% female and 49% male. Average age was 41 years (range 22-73). Most common primary location was lower extremity (38%), followed by pelvis (35%), upper extremity (14%), spine (8%), and head/neck (5%). Metastasis were present at start of treatment in 14% of pts, involving lung (n = 4) and spine (n = 1). Pts received median of 71 (range 15-139) total doses of denosumab. Dosing interval was increased in 38% (n = 14). With the first interval change, 43% changed to every 6 weeks, 29% every 8 weeks, and 29% every 12 weeks dosing. Most common final dosing interval was 12 weeks (n = 8). 6 pts (16%) had bone complications after mean of 56 doses. This included osteonecrosis of the jaw (n = 4), atypical fracture (n = 1), and non-healing dental wounds (n = 2). All pts with bone complications were treated on the monthly dosing schedule, but there was no statistically significant difference compared to longer intervals (p = 0.22). Pts with GCT progression (n = 10) were either no longer receiving therapy or had missed denosumab doses. There was no statistically significant difference in PFS with standard vs. interval increased dosing (p = 0.97). However, 5-year PFS was superior with interval increased vs standard dosing (p = 0.036). Conclusions: Increasing the interval of denosumab dosing for GCTB provided similar tumor control as compared to standard dosing and is potentially associated with less bone toxicity and more convenience for afflicted pts. Further larger scale studies are needed to better define the optimal interval of denosumab administration in GCTB and the effect on efficacy, toxicity, and associated health care expense.