Oncotarget

Meta-Analysis:

Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis

Kenji Omae _, Yasushi Tsujimoto, Michitaka Honda, Tsunenori Kondo, Kazunari Tanabe, Shunichi Fukuhara and Toshi A. Furukawa

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Oncotarget. 2017; 8:68890-68898. https://doi.org/10.18632/oncotarget.20323

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Abstract

Kenji Omae1,2,3, Yasushi Tsujimoto1, Michitaka Honda4, Tsunenori Kondo3, Kazunari Tanabe3, Shunichi Fukuhara1,2 and Toshi A. Furukawa5

1Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

2Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima 960-1295, Japan

3Department of Urology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan

4Department of Surgery, Southern TOHOKU Research Institute for Neuroscience, Southern TOHOKU General Hospital, 7-115 Yatsuyamada, Koriyama, Fukushima 963-8052, Japan

5Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

Correspondence to:

Kenji Omae, email: omae416@fmu.ac.jp

Keywords: bisphosphonate, bone-modifying agent, denosumab, renal cell carcinoma, zoledronate

Received: June 30, 2017     Accepted: August 06, 2017     Published: August 18, 2017

ABSTRACT

Objective: To determine the comparative efficacy and safety of all available bone-modifying agents (BMAs) for the treatment of bone metastases in patients with advanced renal cell carcinoma (RCC).

Results: Three studies (259 patients) were identified for the systematic review. Two studies that compared zoledronic acid with placebo or no zoledronic acid showed that zoledronic acid reduced the risk of skeletal-related events (SREs) by 68% (pooled hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.19–0.55). The quality of evidence was moderate. The incidence of serious adverse events (AEs) was identical (80%) for both treatment arms in one study and not reported in the other study. In the third study that compared denosumab and zoledronic acid among patients with solid tumors or myeloma, a post-hoc subgroup analysis with individual patient data (155 patients) showed an HR of 0.71 (95% CI: 0.43–1.17) for SREs and a risk ratio of 0.86 (95% CI: 0.68–1.08) for serious AEs for denosumab compared to zoledronic acid.

Materials and Methods: We searched the MEDLINE database, Cochrane Library, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov database up to January 2017 without language restriction. Only randomized controlled trials were included. When relevant data were missing, we contacted the investigators of the original study. The Grading of Recommendation Assessment, Development, and Evaluation approach was used to assess the evidence certainty.

Conclusions: Our moderate-quality evidence indicates that zoledronic acid significantly reduces SREs risk among patients with bone metastases of RCC.


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