Upfront Zoledronic Acid Is Best for AI-Related Bone Loss
By Nick Mulcahy
Medscape Medical News
December 18, 2009 (San Antonio, Texas) — Using intermittent zoledronic acid (Zometa, Novartis) upfront to prevent bone loss among postmenopausal women with breast cancer taking an aromatase inhibitor (AI) is better than delaying the therapy.
This is one of the findings from the final 5-year results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST), which was presented here at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS).
The study is the "longest running trial" testing the hypothesis that zoledronic acid prevents bone loss in these hormone-receptor-positive postmenopausal women who are prescribed an AI, said Adam Brufsky, MD, from the University of Pittsburgh Cancer Institute in Pennsylvania. He was speaking at a meeting press conference over the telephone because illness prevented him from traveling to San Antonio.
"Bone loss and potential fracture are a known complication of breast cancer therapy, including aromatase inhibitors," said Dr. Brufsky.
Zoledronic acid, an intravenous bisphosphonate given in the study over 15 minutes every 6 months, is an alternative to an oral bisphosphonate for the treatment of AI-related bone loss.
At 5 years, patients randomized to the upfront treatment group (n?= 140) had a mean increase in bone mineral density (BMD) of 6.2% in their lumbar spine, compared with a 2.4% decrease in the delayed treatment group (n?= 132). Thus, the absolute difference between the 2 approaches was 8.6%, which is statistically significant (P?< .001).
Dr. Theresa Guise
In the hip area, with upfront treatment, the BMD increase was 2.6%; with delayed treatment, there was a decrease of 4.1%. The absolute difference was a statistically significant 6.7% (P?< .001).
BMD is considered a strong surrogate marker for fracture risk in postmenopausal women.
"This is a very important study," said Theresa Guise, MD, from the Indiana University School of Medicine in Indianapolis, who moderated the press conference, "because aromatase inhibitors are superior to tamoxifen [in the treatment of hormone-receptor-positive, early-stage breast cancer] and skeletal complications can occur."
This represents a step forward in disease prevention.
"This represents a step forward in disease prevention," she summarized, referring to the inhibition of bone loss from an AI, which in this study was letrozole (Femara, Novartis).
Secondary End Points: Fracture Rates and Secondary Recurrences
In this multicenter study, postmenopausal women were eligible if they had estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer (stages?I to IIIA) and hip and lumbar T?scores of –2 or more. The T?score refers to bone density assessed by dual-energy x-ray absorptiometry.
All of the patients underwent surgery, chemotherapy, and/or radiation within 12 weeks of enrolment and had no residual disease.
All participants received letrozole 2.5?mg orally daily. The upfront group (n?= 300) received zoledronic acid immediately after random assignment.
The delayed group (n?= 300) received zoledronic acid when either postbaseline lumbar spine or total hip T?score decreased to less than –2.0 or a nontraumatic clinical fracture occurred.
Although the study was not designed to detect a significant difference in the fracture rate or disease between treatment groups, both were secondary end points.
Fractures occurred in 9.3% (n = 28) of the patients treated upfront and in 11% (n?= 33) of the patients receiving delayed treatment.
There were fracture and disease recurrence data for all 600 study participants, whereas there were only full 5-year BMD data for 262 participants.
In terms of disease recurrence, events occurred in 5.3% (n?= 16) of the patients treated upfront and in 7% (n?= 7) of the patients receiving delayed treatment. Twice as many women in the delayed-treatment group as in the upfront group had distant recurrence (19 vs 9).
Whether or not zoledronic acid can improve disease-free survival is the subject of a major clinical trial, AZURE, said Dr. Brufsky. Early results from the AZURE trial were presented at last year's SABCS conference and covered by Medscape Oncology at that time. Also, Austrian investigators recently published data indicating that zoledronic acid improves disease-free survival in breast cancer.
There were no serious renal events and no osteonecrosis of the jaw, which confirmed that the drug was safe and well tolerated, said Dr. Brufsky.
Dr. Brufsky reports serving as a consultant to Novartis. Dr. Guise reports serving on the advisory boards of Amgen, Lilly, Novartis, and Roche.
32nd Annual San Antonio Breast Cancer Symposium (SABCS): Abstract?4083. Presented December?11, 2009.
