Xalkori® The First Prospectively Identified Precision Medicine for Treatment of Non-Small Cell Lung Cancer (NSCLC): Development Opportunities and Challenges

• Activity Number: 9
• Type: Invited
• Date/Time: Sunday, July 29, 2012 : 2:00 PM to 3:50 PM
• Sponsor: JSM 2012 Host Local Chapter - San Diego
• Author(s): Paulina Selaru*+ and Yiyun Tang and Bo Huang
• Companies: Pfizer Inc. and Pfizer Inc. and Pfizer Inc.
• Keywords: predictive biomarker ; personalized (precision) medicine ; analyses of single-arm studies ; covariate-matched analysis ; covariate- adjusted analysis ; "quasi-randomized" trials

Abstract

For decades, treatment selection for cancer patients has been based on anatomic location and tumor histology. Current thought suggests that lung cancer is not a single disease but consists of disease subtypes that are driven by distinct molecular aberrations. One such aberration, the EML4-ALK gene fusion was identified in 2007. A new treatment is now available for NSCLC patients that have this specific gene fusion as crizotinib (XALKORI®) has received accelerated approval from the U.S. FDA in August 2011. Approval was based on data from 2 phase 1/2 single arm studies that enrolled advanced/metastatic ALK-positive, NSCLC patients. Remarkable anti-tumor activity was observed early on and consistently over time. As a first-in-class and first-on-target agent in a prospectively identified, molecularly enriched population, development of crizotinib posed some unique opportunities and challenges. As the body of evidence for submission included data from single arm studies, we present different methods and analyses (e.g. covariate-matched or adjusted) employed to describe the crizotinib data in a "quasi-randomized" manner relative to historical data from NSCLC patients.