The Medical Research Council (MRC) Myeloma IX is a Phase III, prospective, multicenter, randomized, controlled study to compare intravenous (IV) Zometa (4 mg every 3-4 weeks) with oral clodronate (1600 mg daily) based on the severity of bone disease and in improving survival. A total of 1,960 evaluable patients from the United Kingdom and New Zealand with newly diagnosed International Staging System (ISS) Stage I, II or III multiple myeloma entered either an intensive or non-intensive treatment pathway, determined on the basis of performance status, informed decision and consent. Patients were randomized for type of bisphosphonate therapy and first-line therapy (induction chemotherapy) on a 1:1 basis.

The primary study endpoints were OS, PFS, and response. Overall survival was defined as the length of time from randomization to death due to any cause. Progression-free survival was defined as the length of time from randomization to disease progression or death. Secondary endpoints included SREs (including bone fractures, radiation to bone, surgery to bone, bone lesions and/or spinal cord compression) and safety.

At a median follow-up of 3.7 years, Zometa reduced the relative risk for death by 16% (HR 0.842; 95% CI 0.74-0.96;s benefit on SREs. In an exploratory Cox model including first SRE as a time-dependent covariate, the adjusted improvement in overall survival with Zometa versus clodronate remained statistically significant. The adjusted result indicated that there was a 15% (HR 0.85; CI 0.74-0.97;>

The tolerability profile of Zometa is well-established and results from this study were found to be consistent with the known profile. The incidence of confirmed osteonecrosis of the jaw (ONJ) in the Zometa and clodronate treatment arms was 4.0% and less than 1.0%, respectively. Renal deterioration was reported to be similar between treatment groups.

SOURCE Novartis Pharmaceuticals Corporation