Conference Coverage
CHICAGO – Women with breast cancer and bone metastases previously treated with bisphosphonates can safely reduce the frequency of their zoledronic acid infusions, according to results from the phase III OPTIMIZE-2 study.
At a median follow-up of 11.9 months, the skeletal-related event (SRE) rate, the study’s primary endpoint, was 23.2% with zoledronic acid (Zometa) every 12 weeks and 22% with zoledronic acid every 4 weeks (P = .724).
The upper limit of the 95% confidence interval for the SRE rate difference was 9.8%, which is below the predefined noninferiority margin of 10%, Dr. Gabriel N. Hortobagyi reported at the annual meeting of the American Society of Clinical Oncology.
Patrice Wendling/Frontline Medical News
Dr. Gabriel Hortobagyi
Zoledronic acid, a third-generation bisphosphonate, is used to reduce the risk of SREs such as bone fractures and spinal cord compression in patients with bone metastases from solid tumors, and is approved to be administered every 3-4 weeks by intravenous infusion.
It has safety concerns similar to other bisphosphonates such as atypical fractures, chronic kidney impairment, and osteonecrosis of the jaw, and therefore, less frequent dosing could have distinct advantages, Dr. Hortobagyi, professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston, said during a press briefing highlighting the study.
Dr. Patricia Ganz, professor of medicine at the University of California, Los Angeles, told reporters that for women living with advanced breast cancer and bone metastases, the late-breaking abstract results mean they can spend more time with family and friends and less time in their doctor’s office, with less toxicity and less cost.
"Sometimes we have to add things, but sometimes we have to take away to add value to patients’ care," she said.
The noninferiority, double-blind OPTIMIZE-2 trial enrolled 412 patients with breast cancer and bone metastases and randomly assigned 403 patients to 4 mg intravenous zoledronic acid every 4 weeks or every 12 weeks for 1 year. All participants had received at least nine doses of zoledronic acid or pamidronate prior to study entry. Their average age was 59 years.
The mean skeletal morbidity rate was 0.46 with monthly zoledronic acid and 0.50 with quarterly treatment (P = .854), Dr. Hortobagyi said.
Times to first on-study SRE were also similar in the two arms (Hazard ratio, 1.06; P = .792).
The safety profile was similar in both arms, although there were more kidney-related adverse events in the monthly arm than in the quarterly arm (9.6% vs. 7.9%), he said.
Women dosed monthly had more grade 3/4 adverse events (47.5% vs. 42.6%) and were more likely to stop treatment due to these events (11.6% vs. 8.9%).
Two patients treated monthly developed osteonecrosis of the jaw, whereas none did with quarterly treatment.
Bone marker profiles were similar between arms, Dr. Hortobagyi said. Serum bone-specific alkaline phosphatase was not significantly different at any time point and urinary N-telopeptide/creatinine was significantly different at week 36 only.
Because of study limitations, such as its relatively modest size, and statistical concerns, the inferiority claim should be interpreted with caution, he said. The protocol was revised during the course of the trial including a placebo arm that was dropped because of poor accrual. The sample size was also reduced from 705 to 412 patients based on new data that became available from the ZOOM trial.
As previously reported, ZOOM also demonstrated no difference in skeletal morbidity rate, its primary endpoint, between zoledronic acid dosed quarterly or monthly in women with metastatic breast cancer and bone metastases.
Novartis sponsored the trial. Dr. Hortobagyi disclosed serving as a consultant to Antigen Express, Novartis, and Pfizer, and research funds to his institution from Novartis.