Rapid fluorodeoxyglucose-positron emission tomography (FDG-PET) response to denosumab treatment in patients with giant cell tumour of bone (GCTB): results from two phase 2 trials — ASN Events
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Rapid fluorodeoxyglucose-positron emission tomography (FDG-PET) response to denosumab treatment in patients with giant cell tumour of bone (GCTB): results from two phase 2 trials (#416)

David Thomas 1 , Rodney J Hicks 2 , Keith Skubitz 3 , Sant Chawla 4 , Arthur Staddon 5 , Jacob Engellau 6 , Amy Feng 7 , Bruce A Bach 7
  1. The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, Australia
  2. Peter MacCallum Cancer Centre, Melbourne, Australia
  3. Division of Hematology, Oncology, and Transplantation and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
  4. Sarcoma Oncology Center, Santa Monica, CA, USA
  5. Division of Hematology Oncology, University of Pennsylvania, Philadelphia, PA, USA
  6. Skåne Universitetssjukhus, Lund, Sweden
  7. Amgen Inc, Thousand Oaks, California, USA

Aims: GCTB is a primary osteolytic tumour characterised by local invasiveness and limited non-surgical treatment options. Osteoclast-like giant cells expressing surface RANK, and stromal cells expressing RANK ligand, are features of GCTB. We report sequential FDG-PET as a sensitive early indicator of GCTB response to denosumab from two phase 2 trials.
Methods: Adult or skeletally mature GCTB patients (N=360) received subcutaneous denosumab 120mg on days 1, 8 and 15 and Q4W thereafter. In some centres, combination FDG-PET and CT images were obtained sequentially as part of routine care. All evaluable scans were reviewed by central independent treatment-blinded reviewers.
Results: Paired pre- and post-treatment FDG-PET scans from 26 patients (144 evaluable scans) showed marked reductions in FDG-PET avidity and reductions in standardised uptake values (SUV) early in response to denosumab at the first post-treatment scan (median [Q1, Q3] 68.5 [50, 84] days from first dose). Results for all lesions (n=26 patients; 144 evaluable scans), lung (n=5; 49 evaluable scans), axial skeleton (n=11; 49 evaluable scans) and appendicular skeleton lesions (n=11; 46 evaluable scans) were: 9.8, 6.5, 9.2, and 10.0 for baseline median SUVmax; 2.7, 1.8, 2.7, 4.0 for best on-study median SUVmax; 1.8, 1.4, 1.7, and 2.1 for mean EORTC Standard Uptake; -64%, -64%, -64% and -66% for best SUVmax response (mean % change from baseline). All paired samples showed a best EORTC response of >25% reduction in SUV uptake following initiation of denosumab treatment. Sequential FDG-PET imaging studies revealed a sustained and progressive SUVmax reduction in GCTB lesions with continued denosumab treatment.
Conclusions: This is the largest GCTB FDG-PET imaging data set from an interventional clinical trial reported to date. FDG-PET is a sensitive early indicator of tumour response to denosumab, preceding both cytoreduction (RECIST) and new bone formation/calcification (HU density). Most importantly, denosumab-induced response was sustained for GCTB patients.

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