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

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.