Role of Adjuvant Zoledronic Acid in Endocrine Receptor-Positive Breast Cancer Being Refined

December 2011, Vol 2, No 7

San Antonio, TX—Mounting evidence from randomized controlled trials suggests that zoledronic acid added to hormonal therapy will have its optimal use as adjuvant therapy in postmenopausal women with either medically/surgically induced menopause or age-related menopause. The results of 2 trials were presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

Updated results of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-12) trial showed that zoledronic acid added to adjuvant hormonal therapy improved overall survival (OS) in premenopausal women with endocrine receptor (ER)-positive early breast cancer undergoing ovarian suppression with goserilin plus tamoxifen or anastrozole.

And a post-hoc exploratory analysis of the ZO-FAST trial suggested that adding zoledronic acid to adjuvant letrozole improved disease-free survival, but not OS, in a subset of postmenopausal women with ER-positive breast cancer.

James N. Ingle, MD, Mayo Clinic, Rochester, MN, formal discussant of these trials, said that zoledronic acid should be considered a new standard of care for premenopausal women with ER-positive breast cancer who undergo ovarian suppression with goserilin, but at this time the data do not support routine use of a bisphosphonate in postmenopausal women with ER-positive breast cancer. He said that an exploratory analysis is not Level 1 evidence, which would be needed to establish a standard of care.

ABCSG-12 These updated results confirm the initial results of the trial, according to lead investigator Michael Gnant, MD, Professor of Surgery, Medical University of Vienna, Austria, and President of ABCSG. “The continued success of this treatmentmeanswe can intervene early and still observe persistence of the benefit of treatment.”

The 4-arm trial randomized 1803 premenopausal women with earlystage, ER-positive breast cancer to tamoxifen or anastrozole, or each of these therapies plus 3 years of treatment with zoledronic acid. First results showed significantly improved disease-free survival in 2008. At the San Antonio meeting in 2011, 84-month data showed that zoledronic acid reduced the risk of breast cancer recurrence by 28% and the risk of death by 36%. There were no reports of osteonecrosis of the jaw or renal failure in this study.

New data from an unplanned exploratory analysis of ZO-FAST showed that in the subgroup of postmenopausal women, the addition of zoledronic acid to adjuvant endocrine therapy increased bone mineral density (BMD) and reduced the risk of disease recurrence over the longer term.

In the overall analysis of the trial, which was presented last year at SABCS, the primary end point of the trial (decrease in loss of BMD) was met, and also a 34% decrease in risk of recurrence was observed in patients treated with up-front zoledronic acid, according to lead investigator Richard de Boer, MD, Royal Melbourne Hospital in Victoria, Australia.

ZO-FAST randomized 1050 patients who were receiving letrozole to up-front zoledronic acid every 6 months or delayed zoledronic acid, which was initiated only when patients experienced a fracture or a decline in BMD.

In the exploratory subgroup analysis, women who were menopausal at diagnosis benefited from immediate treatment with zoledronic acid, with a 29% reduced risk of recurrence and a 35% improvement in OS (not a significant difference). This represented an absolute improvement in diseasefree survival of about 3.6% during 5 years.

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