Meta-analysis of clinical trials to assess denosumab over zoledronic acid in bone metastasis
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REVIEW ARTICLE
Meta‑analysis of clinical trials to assess denosumab over zoledronic acid in bone metastasis Jingcheng Chen1,2 · Lei Zhou1 · Xuelian Liu1 · Xue Wen1 · Hui Li1 · Wei Li1 Received: 7 November 2019 / Accepted: 16 July 2020 © Springer Nature Switzerland AG 2020
Abstract Background Bone metastases-induced skeletal complications result in reduced patient survival, lower quality of life, and an increase in healthcare costs. Previously, zoledronic acid (ZA) was the standard choice of treatment for bone metastases, but another drug, denosumab, has also shown promise. However, the clinical utility of these two drugs requires further exploration. Aim of the review Due to the lack of direct comparisons regarding the efficacy of these drugs in both solid tumors and multiple myeloma (MM), we herein tried to conduct a meta-analysis to compare their efficacy in parallel for bone metastases treatment in both solid tumor and MM patients. Methods Multiple databases including Cochrane Library, MEDLINE, EMBASE, and Web of Science were searched to identify randomized controlled trials (RCTs) reported up to March 2019 directly comparing denosumab with ZA in solid tumors and MM. Information about the following events was primarily searched: time to first on-study skeletal-related event (SRE), time to first and subsequent SREs, and overall survival. Information about secondary outcomes including disease progression, pain, health-related quality of life, and adverse events was also recorded. Results Overall, we analyzed data from four distinct RCTs including 7441 patients, and our analysis revealed that patients in the denosumab group had a significantly delayed incidence to the first and subsequent SREs. In addition, denosumab resulted in a higher incidence of hypocalcemia and osteonecrosis of the jaw (ONJ), and a lower incidence of renal toxicity and acute phase reactions, in comparison to ZA. Conclusion Overall, denosumab showed superiority in delaying the first and subsequent SREs, and hence seems to be a promising choice for managing bone metastases in both solid tumors and MM. However, it can induce a higher incidence of ONJ and hypocalcaemia, but these are preventable and manageable effects. Keywords Bone metastasis · Denosumab · Meta-analysis · Randomized controlled trials · Zoledronic acid
Impacts on practice • Denosumab is beneficial for treating bone metastasis in
Introduction
quent SREs.
Bones are commonly involved in different types of advanced cancers, and the incidence of bone metastases is nearly 100% in myeloma, 65–75% in breast or prostate cancer, and 30–40% in lung cancer [1]. Bone metastases can typically lead to a range of complications, including spinal cord compression, pathologic fracture, tumor-related hypercalcemia, pain, and impaired mobility [2, 3]. Among these, skeletal events result in a downgraded quality of life, greater anesthetic use, reduced patient survival, and increased hospitalization and medical resource utilization [4–6]. The therapeutic bone-targeting drugs used to treat skel
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