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Zoledronic acid versus pamidronate in patients with breast cancer and multiple myeloma who are at high risk for skeletal complications.

857 Background: We previously reported the long-term efficacy and safety of 4 mg zoledronic acid (Zol) compared with 90 mg pamidronate (Pam) in patients with breast cancer or multiple myeloma (Rosen et al. Cancer. 2003;98:1735-1744). Because patients who experience a skeletal-related event (SRE) appear to have an increased risk of subsequent SREs, we performed a retrospective exploratory analysis to assess the benefit of zoledronic acid in patients with a history of SREs before study entry.


METHODS
An SRE was defined as pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or hypercalcemia. Patients were retrospectively stratified based on whether they had an SRE before study entry, and the occurrence of SREs on study (over 25 months) was analyzed.


RESULTS
A total of 1,122 patients were randomized to Zol or Pam; 691 completed the 13-month core phase, and 417 entered the 12-month extension phase. Before study entry, 760 (68%) patients had experienced at least 1 SRE, and these patients had a 2-fold higher risk of developing an SRE on study than patients with no prior SRE (hazard ratio = 2.08) Across treatment groups, ∼58% of these patients had at least 1 SRE on study versus only ∼32% patients with no SRE before study entry. Among patients with an SRE before study entry, Zol was significantly more effective than Pam at reducing the occurrence of on-study SREs. Andersen-Gill multiple event analysis showed that Zol reduced the risk of SREs by an additional 20% compared with Pam (risk ratio = 0.8; P = .009). In addition, 54% of patients in the Zol group compared with 62% in the Pam group had an SRE on study (P = .032), and the mean skeletal morbidity rate was 1.23 events/yr in the Zol group versus 1.70 events/yr in the Pam group (P = .026). Zol also significantly delayed median time to first SRE by 3.5 months in this subgroup (296 days versus 196 days for the Pam group; P = .029).


CONCLUSIONS
This exploratory analysis suggests that patients with a history of SREs are at significantly higher risk of subsequent skeletal complications, and Zol was significantly more effective than Pam at reducing SREs in this subgroup. [Table: see text].