Mechanisms of acquired resistance to 3
rd
generation TKIs
•
A number of AR mechanisms identified, C797s-mut, MET amplification,
KRAS-mut…
–
C797S mutation is the most commonly-acquired mutation that confers
resistance to osimertinib
•
Tumor heterogeneity exists
•
Given the heterogeneity of the resistance mechanisms, combination of
EGFRTKIs with other agents required to overcome the diverse resistant
clones
•
New strategies for addressing these AR mechanisms
–
Combination therapies, including cetuximab, MET and MEK inhibitors
–
Compounds targeting C797s-mut
