CHICAGO, IL—In patients with breast cancer who had previously received monthly intravenous bisphosphonate therapy for bone metastases for a year or longer, maintenance zoledronic acid administered every 12 weeks was noninferior to every 4 weeks, the phase 3 OPTIMIZE-2 trial reported at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
Not only was the 12-week schedule efficacious, less frequent administration resulted in fewer renal adverse events (AEs) and no cases of osteonecrosis of the jaw, compared with two cases (1%) in the 4-week arm, said Gabriel N. Hortobagyi, MD, a Professor of Medicine at the University of Texas MD Anderson Cancer Center, Houston, TX. The safety profiles of the two dosing regimens were otherwise similar.
The prospective multicenter trial randomly assigned 412 women who had bone metastases from breast cancer who previously had received nine or more doses of an intravenous bisphosphonate—either zoledronic acid or pamidronate—during the first 10 to 15 months of therapy to zoledronic acid 4 mg intravenously every 4 weeks (n = 206) or every 12 weeks (with a placebo between doses to maintain blind; n = 206), for 1 year.
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Median age of the women was 59.2 years in the zoledronic acid 4-week arm compared with 58.6 years in the 12-week arm.
At a median of 11.9 months of follow-up, proportion of patients with one or more skeletal-related event (SRE) on study—the primary endpoint—was 22% in the 4-week arm and 23.2% in the 12-week arm. The difference in SRE rate between arms was 1.2% (95% CI: –7.5%-9.8%, P = 0.724). The upper limit of the 95% confidence interval, 9.8%, was less than the predefined margin of 10%, indicating noninferiority of zoledronic acid every 12 weeks compared with every 4 weeks, Dr. Hortobagyi reported.
Secondary endpoints included time to first SRE during study; the skeletal morbidity rate (SMR); change in the metabolic bone turnover markers urine N telopeptide (uNTx) and serum bone alkaline phosphatase (BAP); and safety.
Times to first on-study SRE were similar in the zoledronic acid 4-week and 12-week arms (hazard ratio [HR], 1.06; 95% CI: 0.70-1.60, P = 0.792). Mean SMRs were also similar, he reported, 0.46 versus 0.50 (P = 0.854), respectively. Change in bone markers from baseline was significantly different for uNTx creatinine at week 36 only (P = 0.013); for BAP, no significant difference was observed at any time point.
“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,” said Patricia Ganz, MD, FASCO, ASCO Expert, in a press release.
During the course of the clinical trial, protocol revisions included that the placebo arm was dropped early in the study secondary to poor accrual and the sample size was reduced from 705 to 412 based on data that became available. For these reasons, Dr. Hortobagyi said these results should be interpreted with caution.
- Hortobagyi GN, Lipton A, Chew HK et al. Abstract LBA9500. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.