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


METHODS
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 on-study 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.
Complutense University and Hospital General Universitario Gregorio Maranon, Servicio De Oncologia Medica, Madrid, Spain. mmartin@geicam.org
Miguel
M
Martin
Richard
R
Bell
Hugues
H
Bourgeois
Adam
A
Brufsky
Ingo
I
Diel
Alexandru
A
Eniu
Lesley
L
Fallowfield
Yasuhiro
Y
Fujiwara
Jacek
J
Jassem
Alexander H G
AH
Paterson
Diana
D
Ritchie
Günther G
GG
Steger
Alison
A
Stopeck
Charles
C
Vogel
Michelle
M
Fan
Qi
Q
Jiang
Karen
K
Chung
Roger
R
Dansey
Ada
A
Braun
D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069448:Denosumab; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D011788:Quality of Life; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000276:immunology; D000077211:Zoledronic Acid
D061067:Antibodies, Monoclonal, Humanized; D004164:Diphosphonates; D007093:Imidazoles; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab; D000077211:Zoledronic Acid