Zoledronic Acid Found to Shield Bones From Aromatase Inhibitors

SAN ANTONIO — Twice-yearly intravenous zoledronic acid started simultaneously with aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive early-stage breast cancer shows promise as a means of preventing bone loss and even building bone, according to the 2-year results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST).

Z-FAST is an ongoing open-label multicenter randomized trial involving 600 U.S. and Canadian women receiving up to 5 years of adjuvant letrozole (Femara) as part of the treatment of hormone receptor-positive early breast cancer. Participants were randomized to up-front 15-minute infusions of 4 mg of zoledronic acid every 6 months or to the delayed start of bisphosphonate until after a clinical fracture occurred or a patient's bone mineral density (BMD) T score dropped to below 2. Through 24 months, 12.7% of patients in the delayed group had initiated zoledronic acid, Dr. Adam M. Brufsky reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Z-FAST was designed to determine whether up-front zoledronic acid is the superior strategy for prevention of aromatase inhibitor-associated bone loss and fractures. The recently published 1-year Z-FAST results (J. Clin. Oncol. 2006 Dec. 11 [Epubdoi 10.1200/JCO.2005.05.3744]) showed up-front therapy protected against bone loss while the delayed strategy did not.

At 2 years, the gap in efficacy has widened. The mean increase in BMD at the lumbar spine was 3.1% with up-front zoledronic acid, compared with a mean 2.9% decline with delayed therapy. The mean increase in total hip BMD was 1.4% with up-front therapy, vs. a 3.2% drop with delayed therapy. Markers of bone turnover were continuously suppressed in the up-front therapy arm over 24 months, according to Dr. Brufsky of the University of Pittsburgh.

The incidence of clinical fractures through 24 months was 4.3% in the up-front therapy group and 4.0% in the delayed treatment arm. Two cases of renal impairment have occurred in the up-front therapy group, both believed related to zoledronic acid. No cases of osteonecrosis of the jaw have occurred in the 600-patient study.

Dr. Brufsky is a consultant to and member of the speakers' bureau for Z-FAST sponsor Novartis Pharmaceuticals.

SAN ANTONIO — Twice-yearly intravenous zoledronic acid started simultaneously with aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive early-stage breast cancer shows promise as a means of preventing bone loss and even building bone, according to the 2-year results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST).

Z-FAST is an ongoing open-label multicenter randomized trial involving 600 U.S. and Canadian women receiving up to 5 years of adjuvant letrozole (Femara) as part of the treatment of hormone receptor-positive early breast cancer. Participants were randomized to up-front 15-minute infusions of 4 mg of zoledronic acid every 6 months or to the delayed start of bisphosphonate until after a clinical fracture occurred or a patient's bone mineral density (BMD) T score dropped to below 2. Through 24 months, 12.7% of patients in the delayed group had initiated zoledronic acid, Dr. Adam M. Brufsky reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Z-FAST was designed to determine whether up-front zoledronic acid is the superior strategy for prevention of aromatase inhibitor-associated bone loss and fractures. The recently published 1-year Z-FAST results (J. Clin. Oncol. 2006 Dec. 11 [Epubdoi 10.1200/JCO.2005.05.3744]) showed up-front therapy protected against bone loss while the delayed strategy did not.

At 2 years, the gap in efficacy has widened. The mean increase in BMD at the lumbar spine was 3.1% with up-front zoledronic acid, compared with a mean 2.9% decline with delayed therapy. The mean increase in total hip BMD was 1.4% with up-front therapy, vs. a 3.2% drop with delayed therapy. Markers of bone turnover were continuously suppressed in the up-front therapy arm over 24 months, according to Dr. Brufsky of the University of Pittsburgh.

The incidence of clinical fractures through 24 months was 4.3% in the up-front therapy group and 4.0% in the delayed treatment arm. Two cases of renal impairment have occurred in the up-front therapy group, both believed related to zoledronic acid. No cases of osteonecrosis of the jaw have occurred in the 600-patient study.

Dr. Brufsky is a consultant to and member of the speakers' bureau for Z-FAST sponsor Novartis Pharmaceuticals.

SAN ANTONIO — Twice-yearly intravenous zoledronic acid started simultaneously with aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive early-stage breast cancer shows promise as a means of preventing bone loss and even building bone, according to the 2-year results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST).

Z-FAST is an ongoing open-label multicenter randomized trial involving 600 U.S. and Canadian women receiving up to 5 years of adjuvant letrozole (Femara) as part of the treatment of hormone receptor-positive early breast cancer. Participants were randomized to up-front 15-minute infusions of 4 mg of zoledronic acid every 6 months or to the delayed start of bisphosphonate until after a clinical fracture occurred or a patient's bone mineral density (BMD) T score dropped to below 2. Through 24 months, 12.7% of patients in the delayed group had initiated zoledronic acid, Dr. Adam M. Brufsky reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Z-FAST was designed to determine whether up-front zoledronic acid is the superior strategy for prevention of aromatase inhibitor-associated bone loss and fractures. The recently published 1-year Z-FAST results (J. Clin. Oncol. 2006 Dec. 11 [Epubdoi 10.1200/JCO.2005.05.3744]) showed up-front therapy protected against bone loss while the delayed strategy did not.

At 2 years, the gap in efficacy has widened. The mean increase in BMD at the lumbar spine was 3.1% with up-front zoledronic acid, compared with a mean 2.9% decline with delayed therapy. The mean increase in total hip BMD was 1.4% with up-front therapy, vs. a 3.2% drop with delayed therapy. Markers of bone turnover were continuously suppressed in the up-front therapy arm over 24 months, according to Dr. Brufsky of the University of Pittsburgh.

The incidence of clinical fractures through 24 months was 4.3% in the up-front therapy group and 4.0% in the delayed treatment arm. Two cases of renal impairment have occurred in the up-front therapy group, both believed related to zoledronic acid. No cases of osteonecrosis of the jaw have occurred in the 600-patient study.

Dr. Brufsky is a consultant to and member of the speakers' bureau for Z-FAST sponsor Novartis Pharmaceuticals.