Dataset Information

Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumor of bone: A randomized clinical trial.

ABSTRACT:

Background

Although denosumab has been approved as an antiresorptive agent for giant cell tumor of bone, its efficacy has not been proven.

Objectives

To compare the efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable giant cell tumor of bone.

Methods

A total of 250 patients with surgically unsalvageable giant cell tumor of bone were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg per 4 weeks plus an additional 120 mg on days 8 and 15; n = 125) or intravenous zoledronic acid (ZA group; 4 mg per 4 weeks; n = 125) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals.

Results

Denosumab and zoledronic acid had similar tumor responses (p = 0.18) and clinical benefits (p = 0.476). Disease progression was observed in fewer patients in the DB group (1%) than ZA group (2%). Denosumab caused fatigue (p = 0.0004) and back pain (p < 0.0001), while zoledronic acid caused hypocalcemia (p < 0.0001), flu-like symptoms (p = 0.021), hypotension (p = 0.021), and hypokalemia (p = 0.021). Denosumab treatment was markedly more expensive than zoledronic acid treatment (p < 0.0001). The cost to manage treatment-emergent adverse effects was higher for the ZA group than the DB group (p = 0.0425). Overall survival was the same for both treatments (p = 0.066).

Conclusions

Denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable giant cell tumor of bone.

SUBMITTER: Li S

PROVIDER: S-EPMC6357891 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumor of bone: A randomized clinical trial.

Li Shenglong S Chen Peng P Yang Qiankun Q

Journal of bone oncology 20190123

<h4>Background</h4>Although denosumab has been approved as an antiresorptive agent for giant cell tumor of bone, its efficacy has not been proven.<h4>Objectives</h4>To compare the efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable giant cell tumor of bone.<h4>Methods</h4>A total of 250 patients with surgically unsalvageable giant cell tumor of bone were included in this randomized clinical trial. Patients received either subcutaneous denosuma ...[more]

PMID: 30740297

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Project description:IntroductionThe primary analysis of a global phase 3 study that evaluated the efficacy and safety of denosumab versus zoledronic acid for preventing skeletal-related events (SREs) in adults with newly diagnosed multiple myeloma (MM) indicated that denosumab was noninferior to zoledronic acid for time to first on-study SREs. Here we present a subgroup analysis to evaluate efficacy and safety in Asian patients.MethodsPatients were randomized 1:1 to receive denosumab 120 mg subcutaneously or zoledronic acid intravenously 4 mg every 4 weeks in a double-blind, double-dummy fashion. All patients received standard-of-care first-line antimyeloma treatment. Each patient received either study drug until an estimated 676 patients experienced at least one on-study SRE and the primary efficacy and safety analyses were completed.ResultsOf 1718 total enrolled patients, 196 Asian patients (denosumab, n = 103; zoledronic acid, n = 93) were included in this subgroup analysis. Fewer patients in the denosumab group developed first on-study SRE compared with the zoledronic acid group; the crude incidence of SREs at the primary analysis cutoff was 38.8% and 50.5%, respectively (HR [95% CI], 0.77 [0.48-1.26]). All 194 patients receiving at least one dose of study drug experienced at least one treatment-emergent AE. The most common AEs reported in either group (denosumab, zoledronic acid) were diarrhea (51.0%, 51.1%), nausea (42.2%, 46.7%), and pyrexia (38.2%, 41.3%). Treatment-emergent renal toxicity occurred in 9/102 (8.8%) and 20/92 (21.7%) patients, respectively. Similar rates of positively adjudicated osteonecrosis of the jaw (7 [6.9%] vs 5 [5.4%]) and treatment-emergent hypocalcemia (19 [18.6%] vs 17 [18.5%]) were reported in the denosumab and zoledronic acid groups, respectively.ConclusionEfficacy and safety outcomes from this Asian subgroup were comparable to those of the full study population. Overall, this analysis supports denosumab as an additional treatment option for standard of care for Asian patients with newly diagnosed MM with lytic bone lesions.Clinical trial registrationClinicalTrials.gov NCT01345019.

Project description:Background: Metastatic bone disease (MBD) presents significant challenges in patient management, leading to skeletal-related events (SREs), compromised health-related quality of life, and heightened pain experiences. Denosumab (Dmab) and zoledronic acid (ZA) are bone-modifying agents (BMAs) commonly employed to mitigate the sequelae of MBD. Previous meta-analyses have assessed primary outcomes such as overall survival, pathological fractures, radiation to bone, and the time to SREs within studies. However, a single comprehensive analysis comparing their efficacy across multiple primary and secondary outcomes, as well as cost-effectiveness in specific cancer types, has not yet been conducted. Methods: A literature search identified relevant randomized controlled trials (RCTs), and the primary outcomes included overall survival, pathologic fractures, radiation to bone, and the time to SREs within studies. Secondary outcomes included adverse events, pain, analgesia usage, quality of life, and cost. Results: Meta-analysis revealed that Dmab effectively reduced the need for bone-targeted radiation therapy and was superior to ZA in delaying the time to SREs, except in multiple myeloma. Dmab also reduced pathological fracture incidences in breast cancer patients by 39%. Conclusions: Our analysis suggests that while both agents similarly impact overall survival and disease progression, Dmab offers advantages in SRE reduction and improved HRQoL and pain outcomes with lower rates of opioid usage, albeit with higher risks of hypocalcemia and osteonecrosis in some subgroups. The consensus on cost-effectiveness is mixed and varies based on the cancer type and healthcare system, with some studies favoring Dmab's superior efficacy and safety, while others find ZA more cost-effective due to its lower cost. This study underscores the potential of Dmab as a preferred BMA for MBD management, especially for high-risk skeletal complications, while highlighting cancer-specific safety considerations. Further research is warranted to refine cancer-specific BMA use and optimize MBD management strategies.

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Dataset Information

Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumor of bone: A randomized clinical trial.

Background

Objectives

Methods

Results

Conclusions

Publications

Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumor of bone: A randomized clinical trial.

Similar Datasets

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