Skip to main content
main-content
Top

30-01-2019 | Non-small cell lung cancer | News

MET copy number gain insignificant for TKI response in EGFR-positive NSCLC

medwireNews: The level of mesenchymal epithelial transition factor (MET) copy number gain (CNG) does not affect response to tyrosine kinase inhibitors (TKI) in patients with metastatic epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), research shows.

Using MET fluorescence in situ hybridization (FISH), Daniel Tan (National Cancer Centre Singapore) and colleagues showed that an “unexpectedly high” proportion (26%) of 200 consecutive treatment-naïve patients with metastatic EGFR-positive NSCLC had a high MET CNG at time of diagnosis (≥5 plus a MET/centromere 7 ratiο ≥2 for amplification).

The median CNG was 7.6 copies, 23% had MET polysomy, and 3% had MET amplification.

As reported in the Journal of Clinical Oncology, the median time to treatment failure (TTF) did not differ significantly between the MET-high and MET-low patients at 12.2 and 13.1 months, respectively.

There was also no significant difference in response rates between the two groups, at 74.4% and 53.9% for MET-high and MET-low, respectively, and changing the CNG threshold did not change the outcome.

“With early MET inhibitor trials yielding disappointing results, our study suggests that selecting for high MET copy number thresholds alone—for example, five or more—may not be clinically relevant in the context of a dominant oncogene-driven tumor, especially as MET CNG often coexists with other driver alterations,” Tan and co-authors write.

Among a subset of patients who underwent postprogression biopsies, loss of MET was detected in three of six who were initially MET-high, whereas only one of 17 patients identified as MET-low became MET-high.

“Taken together, our data support the conclusion that MET-high is frequently subclonal at the outset and is not always a dominant driver, particularly in the context of EGFR-mutant–positive NSCLC,” the researchers remark.

They add that their results indicate that “the selection pressure imposed by EGFR TKIs did not consistently enrich for MET-high status, likely because of the equivocal functional impact of MET defined solely by a threshold of five or more copies.”

The team also notes that concordance between FISH and next-generation sequencing was low, with just eight of 18 MET-high patients by FISH deemed to have MET CNG by next-generation sequencing.

“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,” Tan et al conclude.

They suggest: “[A] practical clinical algorithm might be to perform MET FISH in patients who demonstrate suboptimal response to initial monotherapy EGFR TKI.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

Related topics