Gefitinib from Phase I Responses to a Personalized Medicine

• 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): Anna Osmukhina*+ and Andrew Stone
• Companies: AstraZeneca and AstraZeneca
• Keywords: personalized medicine ; clinical trials ; targeted therapy ; oncology

Abstract

This presentation will describe the history of the development and regulatory approval of gefitinib (IRESSA) from the identification of early durable responses in phase I to the finding that the presence of activating mutations of EGFR-TK was predictive for efficacy amongst locally advanced or metastatic NSCLC patients. In the period between, phase II monotherapy trials within an unselected advanced NSCLC population confirmed the presence of responses in 12-18% of patients. However, subsequent confirmatory trials in combination with chemotherapy in first-line patients and placebo-controlled monotherapy trials in refractory patients did not demonstrate a statistically significant survival benefit. Subgroup analyses from these and other trials suggested that increased activity was associated with particular clinical characteristics and in parallel, hypotheses had been generated that the efficacy was associated with biological factors. This lead to the design and analysis of the IPASS study in a clinically selected Asian population which demonstrated that activating mutations of EGFR-TK were the strongest predictor for the benefit of gefitinib.