The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: results of a 4-week, double-blind, randomized, controlled trial.

Abstract

BACKGROUND:

Metastatic bone disease (MBD) is a frequent complication in patients with breast cancer and is associated with significant morbidity. This study assessed the pharmacokinetics, efficacy, and safety of odanacatib, a selective Cat K inhibitor, in reducing markers of bone resorption in women with breast cancer and MBD.

PATIENTS AND METHODS:

Women with breast cancer and MBD were randomized 2:1 (double-blind) to oral odanacatib 5 mg daily for 4 weeks or intravenous (I.V.) zoledronic acid (ZA) 4 mg given once at study initiation. Plasma samples were collected for pharmacokinetic analysis. Bone resorption was assessed by measuring urinary N-telopeptide of type I collagen corrected for creatinine (uNTx; primary objective, pmol BCE/µmol creatinine). Adverse events (AEs) were monitored throughout the 4-week study and up to 14 days after last dose.

RESULTS:

A total of 43 patients (mean age, 60 years) received odanacatib (n = 29) or ZA (n = 14); 40 patients completed 4 weeks of treatment. The mean percent change in uNTx values at week 4 was -77% (95% CI, -82 to -71; odanacatib) and -73% (95% CI, -80 to -62; ZA). Mean (standard deviation) plasma concentration of odanacatib was 511.7 (202.9) nM; the range was 63.7-844.8 nM. The most common AEs were nausea, vomiting, headache, and bone pain, which were generally not attributed to study drug.

CONCLUSION:

Odanacatib suppressed uNTx similarly to ZA after 4 weeks of treatment in women with breast cancer and MBD. Odanacatib was generally safe and well tolerated. These results suggest that Cat K inhibition is a potentially important, novel therapeutic approach for treating MBD.

• Authors: Anders Bonde Jensen, Christopher Wynne, Guillermo Ramirez, Weili He, Yang Song, Yuliya Berd, Hongwei Wang, Anish Mehta, Antonio Lombardi
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 10 Issue 6 Pg. 452-8 (Dec 01 2010) ISSN: 1938-0666 [Electronic] United States
• PMID: 21147688 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Biphenyl Compounds
• Bone Density Conservation Agents
• Collagen Type I
• Diphosphonates
• Imidazoles
• Zoledronic Acid
• Cathepsin K
• odanacatib

Topics

• Adult
• Biomarkers (urine)
• Biphenyl Compounds (adverse effects, blood, pharmacokinetics, therapeutic use)
• Bone Density Conservation Agents (adverse effects, blood, pharmacokinetics, therapeutic use)
• Bone Neoplasms (drug therapy, secondary)
• Bone Resorption (drug therapy)
• Breast Neoplasms (drug therapy, pathology)
• Cathepsin K (antagonists & inhibitors)
• Collagen Type I (urine)
• Diphosphonates (therapeutic use)
• Double-Blind Method
• Female
• Humans
• Imidazoles (therapeutic use)
• Middle Aged
• Treatment Outcome
• Zoledronic Acid