Retrospective database analysis of the effect of zoledronic acid on skeletal-related events and mortality in women with breast cancer and bone metastasis in a managed care plan.

BACKGROUND: Bone metastases are common in patients with advanced breast cancer, and place patients at risk for skeletal-related events (SREs) including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and the need for radiotherapy and/or surgery to bone. These SREs are associated with reduced survival and quality-of-life. The nitrogen-containing bisphosphonates Zometa (zoledronic acid, ZOL) and Aredia (pamidronate disodium, PAM) reduce SRE risk in patients with bone metastases from breast cancer. This database analysis compared SRE and mortality rates in a real-life setting in women with breast cancer receiving ZOL and PAM, and assessed long-term ZOL benefit. METHODS: A retrospective, claims-based analysis was conducted using commercial and Medicare Advantage data from >45 US managed-care plans. Eligible adult patients had diagnoses for breast cancer and bone metastasis between 01/01/01 and 12/31/06, continuous enrollment in the health plan, and no evidence of bone metastasis or intravenous bisphosphonate (IV-BP) use for 6 months before their first ZOL or PAM infusion. Patients were followed until disenrollment (including mortality) or end of the analysis period (12/31/07). Persistency was defined as absence of a >45-day gap between IV-BP treatments. RESULTS: Of 8757 patients (mean age, 58.1 [SD 12.4] years), approximately 30% were treated with ZOL, 15% with PAM, and 55% with no IV-BP. Patients treated with ZOL had a moderately lower incidence of SREs (mean, 36.2 vs 40.0 SREs/100 person-years; p = 0.0707) and significantly lower mortality (mean, 6.5 vs 11.2 deaths/100 person-years; p < 0.001) compared with PAM-treated patients. Longer persistency with ZOL was associated with lower risk of fracture and all SREs (trend-test p = 0.0076 and p = 0.0200, respectively). LIMITATIONS: Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as imbalances in patient populations and the potential for bias in treatment selection. CONCLUSIONS: This analysis suggests that fewer than half of breast cancer patients with bone metastases receive IV-BPs. Longer persistence with ZOL was associated with lower SRE risk, and ZOL-treated patients had longer survival and a non-significant trend toward fewer SREs compared with PAM.