Evaluation of Soluble KIT as a Potential Surrogate Marker for Time-to-Tumor Progression in Patients with Advanced GIST by Several Recently Proposed Methods

• Activity Number: 154
• Type: Contributed
• Date/Time: Monday, July 30, 2007 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Xin Huang*+ and Sam DePrimo and Jenny Zhang and Charles Harmon and John Smeraglia and Chuck Baum and Randy Allred
• Companies: Pfizer Inc. and Pfizer Inc. and Harvard University and Pfizer Inc. and Pfizer Inc. and Pfizer Inc. and Pfizer Inc.
• Keywords: biomarker ; clinical trial ; surrogate

Abstract

Researchers are interested in exploring biomarkers that may act as surrogate endpoints for the primary clinical endpoints in clinical trials. A considerable number of statistical methods have been proposed for this topic recently. Sunitinib is a multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, RET and FLT3, approved for the treatment of imatinib-resistant/-intolerant gastrointestinal stromal tumor (GIST). Preliminary analysis in a sunitinib Phase I/II GIST study suggests that a decline in plasma soluble KIT (sKIT) levels correlates with clinical benefit. In this paper, we evaluated the potential of sKIT as a surrogate endpoint for time-to-tumor progression (TTP) using data obtained in a randomized, double-blind, placebo-controlled phase III study of sunitinib in patients with imatinib-resistant/-intolerant GIST by several recently proposed methods.