Zoledronic acid ups PFS in younger early-stage pts

CHICAGO—Zoledronic acid (Zometa) and adjuvant endrocrine therapy lowered the risk of disease recurrence in premenopausal women with early-stage breast cancer, according to the results of a major European trial. The bisphosphonate is already used to prevent bone loss in women undergoing adjuvant endocrine therapy for breast cancer.

“Zoledronic acid significantly improves clinical outcomes beyond those achieved with endocrine therapy alone,” Michael Gnant, MD, president of the Austrian Breast and Colorectal Cancer Study Group (ABCSG), said at the ASCO 2008 plenary session (abstract LBA-4).

The trial was designed to answer two questions, Dr. Gnant said during an ASCO press conference: “First, can aromatase inhibitors [AIs] improve the outcome of breast cancer patients compared with tamoxifen(Drug information on tamoxifen) even in premenopausal patients? Second, can the bisphosphonate zoledronic acid(Drug information on zoledronic acid) improve the clinical outcome in patients when added to adjuvant endocrine treatment?”

For the ABCSG-12 study, 1,803 premenopausal stage I-II patients undergoing goserelin(Drug information on goserelin) (Zoladex)-induced ovarian suppression after surgery were enrolled. The majority of the women did not receive chemotherapy, except for about 5% who had preoperative chemotherapy, said Dr. Gnant, professor of surgery, Medical University of Vienna.

The subjects were treated with tamoxifen alone or anastrozole(Drug information on anastrozole) (Arimidex) alone, or with either endocrine therapy with or without zoledronic acid (single dose of 4 mg IV every 6 months) for 3 years. The median follow up is over 5 years.

There was no difference between tamoxifen and anastrozole in disease-free, recurrence-free, or overall survival, “possibly because of the dominant effect of ovarian suppression with goserelin in premenopausal patients,” he said.

Endocrine therapy plus zoledronic acid reduced the risk of disease-free survival events by 36%, compared with endocrine therapy alone (P = .011). Adding the bisphosphonate to the endocrine treatment regimen also reduced the risk of relapse-free survival events by 35% (P = .015), Dr. Gnant reported.

Zoledronic acid reduced events in categories besides bone metastases, such as locoregional occurrence, distant non-bone metastases, and lesions in the contralateral breast. He suggested that zoledronic acid may be causing a hostile environment for the tumor and killing micrometastases elsewhere in the body.