Breast-Cancer Adjuvant Therapy with Zoledronic Acid

Robert E. Coleman, M.B., B.S., M.D., Helen Marshall, M.Sc., David Cameron,
M.B., B.S., M.D., David Dodwell, M.B., Ch.B., M.D., Roger Burkinshaw,
B.Sc., Maccon Keane, M.D., Miguel Gil, M.D., Stephen J. Houston, M.B.,
B.S., M.D., Robert J. Grieve, M.B., Ch.B., Peter J. Barrett-Lee, M.B.,
B.S., M.D., Diana Ritchie, M.B., Ch.B., M.D., Julia Pugh, C.I.M.Dip.,
Claire Gaunt, B.Sc., Una Rea, B.Sc., Jennifer Peterson, B.App.Sc.,
Claire Davies, B.Sc., Victoria Hiley, B.Sc., Walter Gregory, Ph.D., and
Richard Bell, M.B., B.S. for the AZURE Investigators

September 25, 2011
(10.1056/NEJMoa1105195)

Abstract

Background

Data suggest that the adjuvant use of bisphosphonates reduces rates of
recurrence and death in patients with early-stage breast cancer. We
conducted a study to determine whether treatment with zoledronic acid,
in addition to standard adjuvant therapy, would improve disease outcomes
in such patients.

Methods

In this open-label phase 3 study, we randomly assigned 3360 patients to
receive standard adjuvant systemic therapy either with or without
zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks
for 6 doses and then every 3 to 6 months to complete 5 years of
treatment. The primary end point of the study was disease-free survival.
A second interim analysis revealed that a prespecified boundary for
lack of benefit had been crossed.

Results

At a median follow-up of 59 months, there was no significant between-group
difference in the primary end point, with a rate of disease-free
survival of 77% in each group (adjusted hazard ratio in the zoledronic
acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79).
Disease recurrence or death occurred in 377 patients in the zoledronic
acid group and 375 of those in the control group. The numbers of deaths —
243 in the zoledronic acid group and 276 in the control group — were
also similar, resulting in rates of overall survival of 85.4% in the
zoledronic acid group and 83.1% in the control group (adjusted hazard
ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid
group, there were 17 confirmed cases of osteonecrosis of the jaw
(cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9
suspected cases; there were no cases in the control group. Rates of
other adverse effects were similar in the two study groups.

Conclusions

These findings do not support the routine use of zoledronic acid in the
adjuvant management of breast cancer. (Funded by Novartis
Pharmaceuticals and the National Cancer Research Network; AZURE Current
Controlled Trials number, ISRCTN79831382.)
Read the article: http://bit.ly/oDOscH

Pharmakon

domingo, 25 de setembro de 2011