How do you approach a patient with discordant mutation testing in liquid vs tissue biopsy for mNSCLC?

The recent advent of liquid biopsy testing for patients with advanced non-small cell lung cancer has generated a tremendous amount of enthusiasm and has altered the diagnostic algorithm for patients. We now have data that shows that liquid biopsies are reliable, are accurate, and can inform treatmen...

If a targetable alteration is observed in one or the other, start therapy based on the positive results whether it is in the blood or tissue.

If I detect ALK on one or the other, I still treat with an ALK inhibitor, as the Venn diagrams for liquid and tissue are known to overlap, but not completely, and the data would suggest similar response rates regardless of how the genomic alteration is detected.

This is a rare occurrence that we see sometimes. The important baseline fact to remember is that these drivers are almost always mutually exclusive in the absence of selective pressure (like treatment). So if you see two mutations on ctDNA that are classical "drivers," I would worry more that you ha...