Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: Results of the OPTIMIZE-2 trial.

LBA9500^ Background: Zoledronic acid (ZOL, 4 mg) every (q) 4 wk reduces the risk of skeletal-related events (SREs) in patients (pts) with bone metastases from breast cancer (BC). The OPTIMIZE-2 trial examined whether ZOL q12 wk was non-inferior to ZOL q4 wk in pts who had previously received monthly IV bisphosphonate (BP) therapy for ~1 year or longer. Methods: This was a prospective, randomized, double-blind, multicenter trial in female pts with bone metastases from BC who previously received ≥9 doses of IV BP (ZOL or pamidronate) during the first 10-15 months of therapy. Pts were randomized (1:1) to receive ZOL 4 mg IV q4 wk or q12 wk (placebo between ZOL doses to maintain blind) for 1 year. The primary endpoint was the proportion of pts with ≥1 SRE on study (SRE rate). Primary analysis was non-inferiority (pre-defined margin of 10%) for the difference in SRE rates. Secondary endpoints included time to first SRE, skeletal morbidity rate (SMR), bone pain score, change in bone turnover markers, and safety. Results: 403 pts were randomized to ZOL q4 wk (n = 200) or q12 wk (n = 203). Median age was 59 years, and baseline characteristics were similar between arms. The SRE rate was 22% and 23.2% in the ZOL q4 and q12 wk arms, respectively. The difference in SRE rate between arms was 1.2% (95% CI, –7.5% to 9.8%; P = .724). The upper limit of this 95% CI (9.8%) is less than the predefined margin of 10%, which indicates non-inferiority of ZOL q12 wk vs q4 wk. Times to first on-study SRE (HR, 1.06; 95% CI, 0.70 to 1.60; P = .792) were similar in the ZOL q4 and q12 wk arms, and mean SMRs were also similar (0.46 vs 0.50, respectively; P = .854). Overall, changes from baseline in bone turnover markers, and the incidence of treatment-emergent adverse events (TEAEs), were similar in the 2 arms. Numerically more renal TEAEs were reported in the ZOL q4 wk vs q12 wk arm (9.6% vs 7.9%, respectively). Two cases (1.0%) of osteonecrosis of the jaw (ONJ) were reported in the q4 wk arm. Conclusions: Among pts who had received monthly IV BP therapy for 1 year or longer, the efficacy of continuing ZOL for an additional year at q12 wk was non-inferior to ZOL q4 wk. Fewer renal AEs and none of the ONJ events were observed in the ZOL q12 wk vs ZOL q4 wk arm. Clinical trial information: NCT00320710.