Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: Analysis based on prior history of skeletal complications

Abstract

7226 Background: We previously reported the efficacy and safety of 4 mg zoledronic acid in patients with bone metastases secondary to lung cancer or other solid tumors (Rosen et al. J Clin Oncol. 2003;21:3150–3157). We report here the results of a retrospective exploratory analysis to assess the risk of skeletal-related events (SREs) and the efficacy of 4 mg zoledronic acid compared with placebo based on patients' history of SREs prior to study entry. Methods: An SRE was defined as a pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or hypercalcemia. Patients were stratified based on their history of SREs before study entry, and the occurrence of SREs on study (over 21 months) was analyzed. Results: A total of 507 patients were randomized to 4 mg zoledronic acid or placebo; 131 completed the 9-month core phase, and 69 entered the 12-month extension phase. Before study entry, 347 (68%) of patients experienced at least 1 SRE, and these patients were at higher risk of developing an SRE on study than patients with no prior SRE (hazard ratio = 1.43). In the placebo group, 52% of patients with a prior SRE had at least 1 SRE on study compared with only 40% of patients with no prior SRE. Among patients with an SRE before study entry, Andersen-Gill multiple event analysis showed that zoledronic acid significantly reduced the risk of developing an SRE on study by 31% compared with placebo (risk ratio = 0.688; P = .009). Zoledronic acid also significantly reduced the mean skeletal morbidity rate (1.96 versus 2.81 SREs/year for placebo; P = .030) and prolonged median time to first on-study SRE by nearly 4 months (215 versus 106 days for placebo; P = .011). Among patients with no SRE before study entry (n = 156), zoledronic acid reduced the risk of SREs by 23% (P = .308), reduced the mean skeletal morbidity rate (1.34 versus 2.53 SREs/year for placebo; P = .332), and prolonged the median time to first SRE by 2.5 months (P = .534). Conclusions: This exploratory analysis demonstrates that patients with a history of SREs are at high risk of subsequent SREs, and zoledronic acid reduces skeletal morbidity regardless of a prior history of SREs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis