Denosumab versus bisphosphonates in patients with advanced cancers-related bone metastasis: systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Bone metastasis is reported to be associated with poor quality of life, and increased risk of hospitalization. We aim to synthesize evidence from published randomized controlled trials (RCTs) which compared the efficacy of denosumab versus bisphosphonates in patients with advanced cancers. Methods: We searched for all published RCTs in the following electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. Retrieved records were screened for eligibility. Time-to-event data were pooled as hazard ratio (HR) using the generic inverse-variance method and dichotomous data were pooled as relative risk (RR) in a random-effect model. We used Review Manager 5.3 for windows. Results: Six unique RCTs with a total of 7722 patients were included. Overall effect estimates favored denosumab group in comparison to intravenous (IV) bisphosphonates in the following terms: time to first skeletal-related events (HR 0.92, 95% CI [0.86, 0.98], p = 0.01), time to subsequent skeletal-related event (RR 0.92, 95% CI [0.86, 0.99], p = 0.03), and radiation to bone (RR 0.81, 95% CI [0.71, 0.92], p = 0.02). Denosumab group was associated with increased risk of grade 3 or 4 hypocalcaemia (RR 1.99, 95% CI [1.11, 3.54], p = 0.02) and reduced risk of renal impairment or toxicity (RR 0.75, 95% CI [0.61, 0.91], p = 0.003) in comparison to IV bisphosphonates group. Pooled studies were homogenous. Conclusion: Denosumab showed a favorable significant impact on delaying the time to first skeletal-related event and reducing the incidence of radiation to the bone event in comparison to bisphosphonates, with similar efficacy regarding overall survival and time to disease progression. Further large-scale and long-term studies are needed to clarify the long-term efficacy and safety of both regimens.