Abstract
BackgroundDenosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); however, radiologic assessment of tumors in bone is challenging. The study objective was to assess tumor response to denosumab using three different imaging parameters in a prespecified analysis in patients with GCTB from two phase 2 studies.MethodsThe studies enrolled adults and adolescents (skeletally mature and at least 12 years of age) with radiographically measurable GCTB that were given denosumab 120 mg every 4 weeks, with additional doses on days 8 and 15 of cycle 1. The proportion of patients with an objective tumor response was assessed using either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST), European Organisation for Research and Treatment of Cancer response criteria (positron emission tomography [PET] scan criteria), or inverse Choi density/size (ICDS) criteria. Target lesions were measured by computed tomography or magnetic resonance imaging (both studies), PET (study 2 only), or plain film radiograph (study 2 only).ResultsMost patients (71.6%) had an objective tumor response by at least one response criteria. Per RECIST, 25.1% of patients had a response; per PET scan criteria, 96.2% had a response; per ICDS, 76.1% had a response. 68.5% had an objective tumor response ≥ 24 weeks. Using any criteria, crude incidence of response ranged from 56% (vertebrae/skull) to 91% (lung/soft tissue), and 98.2% had tumor control ≥ 24 weeks. Reduced PET avidity appeared to be an early sign of response to denosumab treatment.ConclusionModified PET scan criteria and ICDS criteria indicate that most patients show responses and higher benefit rates than modified RECIST, and therefore may be useful for early assessment of response to denosumab.Trial registrationClinicalTrials.gov Clinical Trials Registry NCT00396279 (retrospectively registered November 6, 2006) and NCT00680992 (retrospectively registered May 20, 2008).
Highlights
Denosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); radiologic assessment of tumors in bone is challenging
The benefit of denosumab in GCTB has already been established [10, 11]; our results provide clinicians with additional information on imaging and monitoring patients with GCTB treated with denosumab
Modified Positron emission tomography (PET) scan criteria and inverse Choi density/ size (ICDS) criteria showed responses in most patients in our analysis, indicating a substantially higher benefit rate compared to that assessed by modified RECIST
Summary
Denosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); radiologic assessment of tumors in bone is challenging. Surgical resection is the primary curative method for GCTB; aggressive interventions, such as adjuvant therapy with liquid nitrogen or phenol, are often required to decrease morbidity, avoid amputation, and ensure adequate local control [4, 5]. Denosumab (XGEVA®, Amgen Inc., Thousand Oaks, CA, USA), a RANK ligand inhibitor, is a fully human monoclonal antibody approved for the treatment of unresectable GCTB or when resection may result in severe morbidity. Denosumab treatment of GCTB prevents further tumor progression, reduces tumor size, reforms mineralized bone, and increases intralesional bone density [10, 11]
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