Adjuvant Denosumab Fights Breast Cancer Treatment Fracture Risk

Breast cancer treatment-related fracture risk may be reduced by regular injections of denosumab

medwireNews: Adjuvant denosumab trial results indicate that the anti-RANK ligand therapy significantly reduces the risk of fracture in postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy without adding to the burden of toxicity.

“For these patients with modest risk of disease recurrence, to effectively prevent the most serious side-effect of their aromatase inhibitor treatment is highly beneficial, and should be added to clinical practice”, recommend Michael Gnant, from the Medical University of Vienna in Austria, and co-authors in The Lancet. The study was simultaneously presented at ASCO 2015 Annual Meeting in Chicago, USA.

The time to first clinical fracture was significantly delayed in the 1711 patients who were randomly assigned to receive denosumab 60 mg subcutaneous injection every 6 months compared with 1709 patients given placebo, with a hazard ratio (HR) of 0.50, they report.

At 36 months, an estimated 5.0% of the denosumab-treated patients had sustained a fracture compared with 9.6% of controls, and the estimated rates after 84 months were 11.1% and 26.2%, respectively.

Denosumab-treated patients had significantly fewer fractures over follow-up, regardless of whether their baseline bone mineral density (BMD) T-score was normal, with a score of at least –1, (HR-=0.44) or below this threshold (HR=0.57).

Those given denosumab also showed increases in BMD at the 36-month check-up, averaging gains of 10.02% at the lumbar spine, 7.92% at the total hip and 6.51% at the femoral neck – these were significantly greater than those achieved by the controls.

Indeed, just 10% of 230 patients in the denosumab group who were assessed over 36 months showed lumbar spine density loss compared with 74% of 245 assessed controls, and this pattern was also seen at the other BMD measurement sites.

And patients given denosumab did not have significantly greater rate of adverse or serious adverse events than controls, the researchers write.

While agreeing denosumab is “clearly an effective intervention to prevent fracture”, the authors of an accompanying comment await results from the D-CARE trial of adjuvant denosumab to determine whether denosumab offers the same reduced risk of bone metastases and increased breast cancer survival found with bisphosphonate therapy.

“The recently described survival benefit associated with the use of adjuvant bisphosphonates provides an important extra dimension to the treatment of early breast cancer”, write Robert Coleman, from Weston Park Hospital in Sheffield, UK, and Peyman Hadji, from Krankenhaus Nordwest in Frankfurt, Germany.

“[W]e think this approach will take priority in defining the bone-targeted therapy of choice, thereby limiting the place of denosumab in routine clinical care”, they emphasise.


Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2015; Advance online publication 31 May. DOI:

Coleman R, Hadji P. Denosumab and fracture risk in women with breast cancer. Lancet 2015; Advance online publication 31 May. DOI:

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