ASCO 2014: Women With Breast Cancer and Bone Metastasis Can Safely Scale Back Frequency of Zoledronic Acid Dosing
Findings from a phase III randomized study suggest that women with breast cancer and bone metastasis who have received at least nine doses of zoledronic acid over the previous year can safely scale back dosing from every 4 weeks to every 12 weeks without compromising the effectiveness of the bisphosphonate in reducing skeletal-related events. Lower doses also may decrease the risk of adverse events associated with zoledronic acid. Gabriel N. Hortobagyi, MD, Professor of Medicine at The University of Texas MD Anderson Cancer Center in Houston, reported the results of the OPTIMIZE-2 study at the 2014 ASCO Annual Meeting in Chicago (Abstract LBA9500^).
Intravenous zoledronic acid at 4 mg every 3 to 4 weeks is approved by the U.S. Food and Drug Administration to reduce the risk of skeletal-related events. However, there has been limited research—and no evidence-based guidelines—on the optimal treatment schedule after the first year.
Comparable Skeletal Event Rates
The prospective, double-blind, multicenter OPTIMIZE-2 trial included 403 women with bone metastases from breast cancer who had completed at least nine doses of the bisphosphonates zoledronic acid or pamidronate during the past year. Patients were randomly assigned to receive zoledronic acid at 4 mg every 4 weeks vs every 12 weeks for an additional year, with patients receiving placebo between zoledronic acid doses to maintain the study blind. The median age of the patients was 59 years, and the median follow-up was 1 year.
The primary endpoint was the proportion of patients with one or more skeletal-related events, defined as pathologic fractures, spinal cord compression, and the need for surgery or radiotherapy to the bone. The primary analysis was noninferiority, with a predefined margin of 10% for the difference in skeletal-related event rates.
The skeletal event rates were 22% among women receiving zoledronic acid every 4 weeks vs 23.2% for those taking it every 12 weeks, a difference of 1.2% (95% confidence interval [CI] = −7.5% to 9.8%; P = .724), indicating that less frequent treatment was not inferior to monthly treatment. Other efficacy measures, such as time to first skeletal event and bone turnover markers, were also similar between the two groups. There were no differences in pain levels and use of pain medications between the two treatment schedules.
“Due to some design limitations, such as the relatively modest size of the trial, and the assumptions that go with a noninferiority trial, the noninferiority claim should be interpreted with caution,” Dr. Hortobagyi advised at the ASCO press briefing on patient care and quality of life.
Similar Safety Profiles
“Safety profiles were similar between the two zoledronic acid dosing frequencies,” Dr. Hortobagyi reported. “There were fewer adverse events leading to dose adjustment or interruption in the group receiving the less frequent infusions, and renal function impairment was less frequent in the group receiving the drug every 12 weeks.” Osteonecrosis of the jaw occurred in two patients taking zoledronic acid every 4 weeks, but in none of the patients in the 12-week dosing group.
Commenting on the study findings, Patricia Ganz, MD, ASCO expert on breast cancer and palliative care and moderator of the press briefing, said: “What does this mean for patients? It means that they have more time to spend with their family and friends and do the things that they care about, rather than visiting the doctor’s office. It means less toxicity and less cost. So I think this is really part of the value equation for the patient’s care.” Dr. Ganz is Director of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, Los Angeles.
This research was supported by Novartis Pharmaceuticals. Dr. Hortobagyi reported a consultant or advisory role with Novartis and research funding from Novartis. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
