Zoledronic acid improved survival when added to letrozole

Issue: January 2012

2011 San Antonio Breast Cancer Symposium

SAN ANTONIO — Immediate zoledronic acid therapy added to adjuvant letrozole therapy improved OS in women with hormone receptor-positive early breast cancer, according to long-term follow-up of the ZO-FAST trial presented here.

According to study researcher Richard de Boer, MD, of the Royal Melbourne Hospital in Victoria, Australia, earlier data from the ZO-FAST trial showed that immediate zoledronic acid improved bone mineral density (BMD) and prolonged the disease-free survival.

“The 60-month follow-up of the ZO-FAST trial confirms and extends the BMD improvement seen with immediate zoledronic acid as reported at earlier time points,” de Boer said. “As per the improved disease-free survival seen in the ABCSG-12 and AZURE trials, the data support the hypothesis that the anticancer potential of zoledronic acid might be best realized in a low-estrogen environment.”

Postmenopausal women who were receiving letrozole and who had a BMD T-score of –2 or higher were randomly assigned to immediate zoledronic acid (4 mg every 6 months) or delayed zoledronic acid given when the post-baseline T-score was less than –2. The 1,065 patients were followed for disease recurrence and OS for 5 years. After 60 months of follow-up, immediate zoledronic acid reduced the risk for a DFS event by 34% (P=.034).

In an exploratory analysis of women who were postmenopausal for more than 5 years at study entry, immediate zoledronic acid improved DFS and significantly improved OS compared with delayed zoledronic acid. The risk for recurrence was reduced by 29% and the OS improved by 35%.

During the 5 years of treatment, osteonecrosis of the jaw was reported in four patients who received zoledronic acid, and there was no increase in renal adverse events in those who received zoledronic acid.

Disclosure: Dr. de Boer serves on the speakers’ bureau for Novartis.

One thing that is important is that, overall, the event rate was low in both groups. Unfortunately, we do have relapses and deaths, so we’re not doing well enough. One way we might be able to reduce those deaths is to add an adjuvant bisphosphonate. We have to weigh toxicity and cost vs. the benefit. It’s clear in the ZO-FAST trial that we reduced recurrences. There was a trend toward fewer deaths. Zoledronic acid also is nontoxic, which is another important point. It is only given every 6 months, it’s intravenous, and the side effects are minimal. That’s one of the most important points. If this was a new chemotherapy agent that we were testing, we wouldn’t be excited about these kinds of results. We have a small benefit, but little cost in terms of side effects. Economically, we are only giving it every 6 months, so it’s much better than a lot of our new targeted therapies. This trial is important and exciting, and it needs to be put in perspective of the other bisphosphonate trials.

– Julie Gralow, MD
Professor of Medical Oncology, University of Washington School of Medicine

For more information:

De Boer R. #S1-3. Presented at: the 2011 CTRC-AACR San Antonio Breast Cancer Symposium; Dec. 6-11, 2011; San Antonio

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