How are you approaching patients with Stage IV EGFR NSCLC who progress on first line TKI and are found to have retained EGFR mutation as well as MET amplification?

The nuance here is how the MET amplification was detected and defined. Was it through an NGS platform (such as Guardant) or through FISH-based testing? If the latter, what was the MET gene copy number, and what was the ratio of MET/CEP7?

Nonetheless, assuming MET amplification is an accurate bypass signal, my preference is to treat the resistance with a combination of a MET TKI and continue osimertinib. The ongoing SAVANNAH (NCT03778229) and ORCHARD (NCT0394472) trials will hopefully shed light o...

I think it is challenging to give a single answer here as there is a lot of heterogeneity here.

When MET amplification is driving EGFR TKI resistance, that can be overcome by the addition of a MET inhibitor. The INSIGHT 2 study (Tan et al., Journal of Clinical Oncology 2023) included patients with EGFR mutant NSCLC with MET amplification (defined as GCN ≥ 5 or MET/CEP7 ≥ 2 by tissue or MET GCN ≥ 2.3 by liquid) and patients continued osimertinib and added tepotinib. There was activity: RR 43%, mD...