How would you approach metastatic adenocarcinoma of the lung with ROS1 rearrangement by FISH and EGFR mutation by NGS?

It would be exceedingly uncommon to see a patient with lung adenocarcinoma that harbors a ROS1 fusion and activating EGFR mutation concomitantly. It is generally thought that driver mutations such as EGFR, ALK, ROS1, BRAF, RET, MET, HER-2, and KRAS are mutually exclusive. Having said that, there are...

Concomitant EGFR mutation and ROS1 fusion are uncommon. In general, I would rely on the NGS test. It would be important to know if the EGFR mutation is activating. Also if it was a DNA based NGS test then it could miss ROS1 fusion. A thorough review of the test results would be valuable to make a de...

This is an unusual occurrence that has been reported in the literature. Osimertinib is very well tolerated and can usually be safely combined with other TKIs. For this reason, I'd treat with osimertinib + 1st line ROS1 TKI of choice (entrectinib), potentially starting both at a dose reduction.

I agree with Dr. @Dr. First Last's comments in two ways: this is an uncommon scenario, and I would probably use osimertinib as initial therapy (and retest upon progression). In the Lung Cancer Mutation Consortium (LCMC) study (Kris et al., PMID 24846037), the investigators found that 3% of the patie...