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Can <em>MET</em> Copy Number Predict TKI Resistance in <em>EGFR</em> -Mutant NSCLC?

By: Melissa E. Fryman, MS
Posted: Tuesday, March 26, 2019

According to a study by Daniel S.W. Tan, MD, PhD, of the National Cancer Center Singapore, and colleagues, MET copy number does not correlate directly with resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with non–small cell lung cancer (NSCLC). Increased copy numbers of the mesenchymal epithelial transition gene (MET) are often implicated in driving oncogenesis and mediating TKI resistance, but findings from this study, published in the Journal of Clinical Oncology, suggest MET copy number alone is a poor marker for clinical actionability.

In this retrospective analysis, 200 patients with EGFR-mutant metastatic adenocarcinoma were initially included, with 52 patients classified as MET-high (defined as copy number greater than or equal to 5) and 148 patients classified as MET-low. Of these 200 patients, 154 (39 MET-high and 115 MET-low) were treated with a first-line EGFR TKI and followed until treatment failure.

The median time to treatment failure was 12.2 months versus 13.1 months for the MET-high and MET-low groups, respectively (P = .556). The response rate was 74.4% versus 53.9%. Among patients for whom the time to treatment failure was 6 months or less, no enrichment for MET-high patients was seen. In patients with MET amplification (defined by the MET/centromeric portion of chromosome 7 ratio being greater than or equal to 2), response to an EGFR TKI was attenuated, with the time to treatment failure ranging from 1.0 to 6.4 months. Furthermore, the addition of a MET inhibitor in one patient with MET amplification was effective.

“Moving forward, identifying the appropriate setting for combination with MET inhibitors in EGFR-mutant–positive NSCLC will require increasingly nuanced molecular screening strategies and well-designed clinical trials,” concluded the authors.

Disclosure: The study authors’ disclosure information may be found at ascopubs.org.



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