Denosumab versus zoledronic acid to prevent aromatase inhibitors-associated fractures in postmenopausal early breast cancer; a mixed treatment meta-analysis.

BACKGROUND: A mixed treatment analysis of the comparative effectiveness of denosumab versus zoledronic acid in the prevention of fractures in early postmenopausal breast cancer patients treated with aromatase inhibitors has been conducted.
METHODS: Eligible studies included randomized studies evaluating adjuvant immediate denosumab or immediate zoledronic acid versus delayed treatment for patients with postmenopausal early breast cancer on adjuvant aromatase inhibitors.
RESULTS: At 12 months cutoff, the risk of fractures is not different between immediate treatment (denosumab or zoledronic acid) vs. delayed treatment [OR: 0.78 (95% CrI 0.48 - 1.38) and 0.88 (95% CrI 0.46 - 1.58); respectively]. On the other hand, at the 36 months cutoff, the risk of fractures is reduced for immediate denosumab compared to delayed treatment while it was not decreased for immediate zoledronic acid versus delayed treatment [OR: 0.50 (95% Crl 0.33-0.75) and 0.91 (95% Crl 0.56-1.44) respectively]. For immediate denosumab versus zoledronic acid, there was a significant difference when analyzed by fixed effects models but not by random effects model [OR: 0.55 (95% Crl 0.33-0.89) and 0.55 (95% Crl 0.30-1.04) respectively].
CONCLUSION: This analysis demonstrated that in postmenopausal patients receiving adjuvant aromatase inhibitors, immediate denosumab decreases the risk of fractures compared to delayed treatment at the cutoff of 36 months. Immediate zoledronic acid, however, does not provide the same level of fractures' protection in this category of patients.