Slide 1

Mechanisms of resistance to EGFR TKIs and related treatment strategies Rafal Dziadziuszko Medical University of Gdask, Poland 16th European Congress Perspectives in Lung Cancer Torino, 06 07 March 2014 Slide 2 Disclosure Astra-Zeneca Roche Boehringer-Ingelheim Pfizer Clovis Oncology Slide 3 Currently used EGFR TKIs Gefitinib and erlotinib (reversible, 1st generation EGFR TKIs) Afatinib and dacomitinib* (irreversible, 2nd generation EGFR TKIs) CO-1686* and AZD9291* (Irreversible, 3rd generation mutation-specific EGFR TKIs) * Investigational Slide 4 When should we exepect relapse? Slide 5 First-line trials of EGFR tyrosine kinase inhibitors vs. chemotherapy in pts with EGFR mutations EGFR TKI ComparatorN (Total) EGFR mut- positive Response rate (%) Progression-free survival (months) IPASS 1,2 GefitinibCarboplatin/ paclitaxel 121726171 vs 47 p=0.0001 9.5 vs 6.3 HR 0.48 (0.36 0.64) First-SIGNAL 3 GefitinibGemcitabine/ cisplatin 3094285 vs 38 p=0.002 8.0 vs 6.3 HR 0.54 (0.271.10) NEJ002 4 GefitinibCarboplatin/ paclitaxel 224 74 vs 31 p