Interim safety data on the ZICE trial: A randomized phase III, open-label, multicener, parallel group clinical trial to evaluate and compare the efficacy, safety profile, and tolerability of oral ibandronate versus intravenous zoledronate in the treatment of patients with breast cancer with bone metastases.

Abstract

1085 Background: The IV bisphosphonate zoledronate is widely used in the UK to treat metastatic bone disease from breast cancer. Oral bisphosphonates may have advantages over IV but this has not been formally assessed. Bisphosphonates are associated with renal toxicity and with osteonecrosis of the jaw (ONJ), reported to affect approximately 1% of patients, which is linked to dental infection and tooth extraction. Methods: The Roche Product Limited supported National Cancer Research Institute ZICE trial, coordinated by the Wales Cancer Trials Unit and sponsored by Velindre NHS trust, will determine whether the oral bisphosphonate ibandronate is noninferior to IV zoledronate in terms of preventing skeletally related events (SREs) over 96 weeks in 1,400 patients. Eligible participants must have bone metastases from histologically proven breast cancer and an ECOG performance status 0-2. The primary outcome is frequency and timing of SREs. Secondary outcome measures include time to SRE, proportion with SREs, pain scores, QoL, survival, health resource usage, and serum bone marker levels. Serious adverse events (SAEs) are assessed for expectedness and causality to the bisphosphonate i.e. whether a serious adverse reaction (SAR) or suspected unexpected serious adverse reaction (SUSAR). Results: Recruitment opened in January 2006 and 1,074 patients have been recruited from 98 centers. 231 patients have completed 96 weeks of treatment, an additional 44 have withdrawn and 311 have died. 32 SARs (including 3 ONJ) and 15 SUSARs have been reported. Conclusions: This is the biggest metastatic breast cancer trial conducted in the UK. The IDMC has reviewed all the safety data including the SAE data and has recommended that there are currently no safety concerns. So far, the reported incidence of ONJ is lower than anticipated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche