Endocrine Abstracts

Context: Possible increased risk of malignancy in patients treated with denosumab has been concerned due to inhibition of the immune modulator receptor activator of nuclear factor κ-B ligand.

Objective: To assess the risk of malignancy associated with denosumab treatment.

Data Sources: PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019.

Study Selection: All randomized controlled trials of denosumab (60 mg every 6 months) versus any comparator. Trials using higher drug doses for prevention of skeletal-related events were excluded.

Data Extraction: Data were independently extracted by two reviewers. We used a fixed effect model to pool risk ratios (RR) with 95% confidence intervals (CI).

Data Synthesis:Twenty-five trials (21,523 patients) were included. The risk of malignancy was comparable between denosumab and other comparators (absolute risk difference 0%, RR 1.08 [95% CI, 0.93–1.24], I2 = 0%). Sensitivity analysis based on adequate allocation concealment showed similar results. The risk of malignancy did not differ between groups in any of the subgroup analyses, including stratification by race, individual comparators, indications for treatment and longer drug exposure (≥ 24 months, 9 studies). The risk ratio of cancer-related death was comparable between groups.

Conclusions: Early concerns about a potential increased risk of malignancy resulting from an immune modulatory effect of denosumab are not supported by evidence from 25 RCTs with drug exposure of up to 48 months.