• Chaoyang Chen, Ruoming Li, Ting Yang, Lingyun Ma, Shuang Zhou, Min Li, Ying Zhou, and Yimin Cui.
• Department of Pharmacy, Peking University First Hospital, Beijing, People's Republic of China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
• Clin Ther. 2020 Aug 1; 42 (8): 1494-1507.e1.

PurposeBone metastases from solid tumors and multiple myeloma (MM) represent an important source of morbidity. The present meta-analysis was performed with the purpose of comparing the efficacy and tolerability of denosumab versus zoledronic acid (ZA) in the prevention of skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors or bone lesions in multiple myeloma.MethodsWe searched PubMed, PubMed Central, EMBASE, the Cochrane Library, and ClinicalTrials.gov for relevant studies published until April 23, 2020. We included randomized, controlled trials that investigated the efficacy and tolerability of denosumab 120 mg SC versus ZA 4 mg IV, given every 4 weeks, in patients with bone lesions in multiple myeloma or bone metastases secondary to advanced solid tumors. Two reviewers independently identified studies, assessed the risk for bias, and extracted the data. Times to event outcomes were analyzed using hazard ratios (HRs) and 95% CIs. We analyzed tolerability outcomes using risk ratios (RRs) and 95% CIs, with a fixed-effects model.FindingsFour randomized, controlled trials (7379 patients) were identified as suitable for analysis. The pooled data indicated that denosumab was more favorable than ZA in delaying the time to first on-study SRE (HR = 0.86; 95% CI, 0.80-0.93; P = 0.0001) as well as the time to first and subsequent on-study SREs (HR = 0.83; 95% CI, 0.76-0.90; P < 0.0001); however, the results on overall survival and disease progression were similar between the 2 drugs. Additionally, denosumab was associated with lower risks for bone pain (risk ratio [RR] = 0.88; 95% CI, 0.80-0.97; P = 0.01), osteonecrosis of the jaw (RR = 0.75; 95% CI, 0.61-0.93; P = 0.007), and acute-phase reactions (RR = 0.47; 95% CI, 0.40-0.56; P < 0.00001).ImplicationsCompared with ZA, denosumab demonstrated efficacy in significantly delaying on-study SREs. Furthermore, it showed a better tolerability profile, despite being associated with potential yet manageable adverse events. This study was registered with PROSPERO (identifier: CRD42019126390).Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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