Dr. Scagliotti on Mechanisms of Resistance to EGFR TKIs

Giorgio V. Scagliotti, MD, PhD, head of the Thoracic Oncology Unit, Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Italy, explains the main mechanisms of resistance to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI).

Resistance to EGFR TKIs are caused by two main mechanisms, the first is an EGFR kinase domain mutations called T790M that occurs in approximately 50% of resistance. The second is a C-MET amplification that is present in 20% of cases. As more research is conducted further mechanism of resistance will be discovered.

A number of agents are currently under investigation that can engage the resistant tumors. Trial results were recently released showing a benefit for T790M patients treated with Afatinib (BIBW 2992) and Cetuximab (Erbitux).

This field is constantly involving and new drugs are still under investigation.