Exponential Failure-Time Mixture Model for Evaluating Efficacy in the Presence of a Biomarker: KRAS Validation

• Activity Number: 583
• Type: Contributed
• Date/Time: Wednesday, August 4, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Kallappa M. Koti*+
• Companies: FDA
• Keywords: AFT model ; mixture proportion ; likelihood ratio test ; interaction ; ITT analysis ; identifiability

Abstract

PFS results from the Amgen Study 20020408 were presented and discussed in the December 2008 Oncologic Drugs Advisory Committee. Using the retrospective subgroup analyses it was claimed that KRAS status should be considered when selecting mCRC patients as candidates for panitumumab monotherapy. Similar conclusion was made by Amado et al. (2008). Results based on retrospective "sorted" analyses are not conclusive. We propose an exponential failure-time mixture model that helps to both validate a marker and demonstrate drug efficacy. The model facilitates a comparison of PFS between the wild-type and mutant KRAS subgroups of subjects on the panitumumab arm. The objective of this presentation is to provide details and to discuss the scope and limitation of the proposed methodology. The views expressed here do not necessarily reflect those of the Food and Drug Administration.