Breast-Cancer Adjuvant Therapy with Zoledronic Acid

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.