Bone-related complications and quality of life in advanced breast cancer: Results from a randomized phase III trial of denosumab versus zoledronic acid

Miguel Martin, Richard Bell, Hugues Bourgeois, Adam Brufsky, Ingo Diel, Alexandru Eniu, Lesley Fallowfield, Yasuhiro Fujiwara, Jacek Jassem, Alexander H G Paterson, Diana Ritchie, Günther G. Steger, Alison T Stopeck, Charles Vogel, Michelle Fan, Qi Jiang, Karen Chung, Roger Dansey, Ada Braun

Research output: Contribution to journalArticle

65 Scopus citations


Purpose: Denosumab was shown to be superior to zoledronic acid in preventing skeletal related events (SRE) in patients with breast cancer and bone metastases in a randomized, double-blind phase III study. We evaluated further results from this study related to skeletal complications and health-related quality of life (HRQoL). Experimental Design: Patients were randomized 1:1 to receive subcutaneous denosumab 120 mg (n = 1,026) and intravenous placebo, or intravenous zoledronic acid 4 mg (n = 1,020) and subcutaneous placebo every 4 weeks. Analyses reported here include the proportion of patients with one or multiple onstudy SREs, time to first radiation to bone, time to first SRE or hypercalcemia of malignancy, and change in HRQoL (functional assessment of cancer therapy-general). Results: Fewer patients receiving denosumab than zoledronic acid had an on-study SRE (31% vs. 36%, P = 0.006). The incidence of first radiation to bone was 12% (n = 123) with denosumab versus 16% (n = 162) with zoledronic acid. Denosumab prolonged the time to first radiation to bone by 26% versus zoledronic acid (HR, 0.74; 95% confidence interval [CI], 0.59-0.94, P = 0.012) and prolonged the time to first SRE or hypercalcemia of malignancy by 18% (HR, 0.82; 95% CI, 0.70-0.95; P = 0.007). Ten percent more patients had a clinically meaningful improvement in HRQoL with denosumab relative to zoledronic acid, regardless of baseline pain levels. Conclusions: Denosumab was superior to zoledronic acid in reducing bone-related complications of metastatic breast cancer and maintained HRQoL, providing an efficacious, well-tolerated treatment option for patients with bone metastases from breast cancer.

Original languageEnglish (US)
Pages (from-to)4841-4849
Number of pages9
JournalClinical Cancer Research
Issue number17
Publication statusPublished - Sep 1 2012


ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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