Women with breast cancer, bone metastases can scale back zoledronic acid treatment after 1 year

CHICAGO — Women with breast cancer and bone metastases who successfully complete 1 year of monthly maintenance with zoledronic acid can scale back to quarterly treatment without compromising safety or benefit, according to results of a randomized phase 3 trial presented at the ASCO Annual Meeting.

Perspective from Patricia A. Ganz, MD

“The addition of bisphosphonate drugs like zoledronic acid has dramatically improved the care of patients with bone metastases, but long-term treatment carries the risk of serious side effects, such as osteonecrosis of the jaw and kidney problems,” Gabriel N. Hortobagyi, MD, professor of medicine at The University of Texas MD Anderson Cancer Center, said in a press release. “We found that less frequent treatment may reduce the risk of serious side effects, with added benefits in reduced patient inconvenience and cost.”

Gabriel N. Hortobagyi

The double blind, multicenter OPTIMIZE-2 trial included 403 women with bone metastases from breast cancer who had already undergone about 1 year of monthly treatment zoledronic acid. Hortobagyi and colleagues randomly assigned half of the women to continue monthly zoledronic acid for another year. The remainder of the women received zoledronic acid every 3 months.

Researchers reported skeletal event rates of 22% in the monthly treatment arm and 23.2% among those treated every 3 months, equating to a difference of 1.2% (95% CI, -7.5% to 9.8%). The upper limit of the 95% CI was lower than the predefined margin of 10%, demonstrating the less frequent treatment regimen was noninferior to monthly treatment.

Results showed the time to first skeletal event (HR=1.06; 95% CI, 0.7-1.6) was comparable between those treated monthly and those treated every 3 months. Mean skeletal morbidity rates (0.46 for monthly treatment vs. 0.5 for quarterly treatment; P=.854) and bone turnover markers also were similar between groups.

Still, efficacy data should be interpreted with caution due to design limitations and statistical concerns, according to researchers.

The incidence of renal treatment-emergent adverse events was higher in the monthly group (9.6% vs. 7.9%). Osteonecrosis of the jaw developed in two patients assigned monthly treatment group and none assigned to the less frequent regimen.

For more information:

Hortobagyi GN. Abstract #LBA9500. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: The researchers report research funding and honoraria from, consultant/advisory roles with, expert testimony for, employment/leadership positions with and stock ownership in Novartis.

Perspective

Patricia A. Ganz, MD

Women with metastatic breast cancer who require long-term protection against bone fractures now have the option of receiving maintenance bisphosphonate therapy at less frequent intervals without compromising benefit or safety. This means patients have more time with their families, and [it] also means less toxicity and less costs for patients.

Patricia A. Ganz, MD

Director, cancer prevention and control research

UCLA Jonsson Comprehensive Cancer Center

Disclosures: Ganz reports no relevant financial disclosures.