Waxing and Waning of MET Amplification in EGFR-Mutated NSCLC in Response to the Presence and Absence of Erlotinib Selection Pressure.

Somatic sensitizing mutations in the epidermal growth factor receptor (EGFR) are associated with response to EGFR tyrosine kinase inhibitors (TKIs), however acquired resistance and subsequent progression of disease inevitably occurs. One such mechanism of acquired resistance (AR), a second site mutation in the EGFR, T790M, has been shown to wax and wane in the presence and absence of selection pressure in the form of EGFR TKI therapy. Another less common mechanism of AR is development of a secondary driver pathway via MET amplification. Here we describe waxing and waning MET amplification in to the presence and absence of erlotinib supporting the idea that mechanisms of AR other than T790M also respond to EGFR TKI selection pressure, with implications for standard practice and clinical trial design.