Abstract Abstract #1157 Background: In breast cancer patients with metastatic bone disease (MBD), an osteolytic process releases factors that sustain tumor cell survival and proliferation. Cathepsin (Cat) K inhibition suppresses osteolysis in preclinical models of MBD. This study assessed the efficacy and safety of odanacatib, a potent and reversible selective Cat K inhibitor, in reducing markers of bone resorption in women with breast cancer and MBD depending on concomitant anti-neoplastic treatment.
 Materials and Methods: Women with breast cancer and MBD were randomized (double-blind) to oral odanacatib 5 mg daily for 4 weeks or IV zoledronic acid (ZA) 4 mg given once at study initiation. Bone resorption was assessed by urinary N-telopeptide of type I collagen corrected for creatinine (uNTx). A post-hoc analysis of the influence of concomitant therapy (chemotherapy vs hormone therapy) on study medication effects on uNTx was also conducted. Adverse events (AE) were monitored throughout the 4-week study and up to 14 days after last dose.
 Results: 43 patients (mean age 60 yrs) received odanacatib (n=29) or ZA (n=14); 40 patients completed all 4 weeks of treatment. 12 (41%) and 17 (59%) patients on odanacatib and 6 (46%) and 7 (54%) patients on ZA received chemotherapy or hormone therapy, respectively; one patient was on both co-therapies and one patient on ZA was not on concomitant therapy. Results for the effect of study medication on uNTx as well as the effects of concomitant therapy on each treatment group are shown in the table; results for the full analysis set were similar. The most common reported AEs were nausea, vomiting, headache, and bone pain, and generally not attributed to study drug.
 Conclusions: In women with breast cancer and MBD, the Cat K inhibitor, odanacatib, suppressed markers of bone resorption after 4 weeks of treatment. Mean uNTx was decreased in both treatment groups. The effect on biomarkers observed in this study was seen irrespective of concomitant anti-neoplastic treatment. Odanacatib was generally safe and well tolerated. These results suggest that Cat K inhibition is a potentially important, novel therapeutic approach for treating MBD.
 
 Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1157.