Mutation Testing for NSCLC in 2017

Transcript:Benjamin P. Levy, MD: There have been tremendous advances in genetic interrogation for lung cancer tumors over the past 5 to 10 years. What we were doing before was just testing for EGFR and ALK rearrangements for non—small cell lung adenocarcinoma. And I think that’s changed over the past 2 to 3 years. There’s a growing list of rare, yet actionable, mutations that we need to test for: BRAF, HER2, ROS rearrangements, RET rearrangements. These are all potentially actionable and should be tested. So, I always make the pitch for both academic and community centers to make sure that they are performing comprehensive genomic profiling, not just testing for ALK rearrangements and EGFR mutations, but testing for a broad spectrum of mutations that may be actionable. I don’t think there are really any differences between academic and community centers. I think everyone has received the word, and the word is comprehensive genomic profiling. My only message would be for those that are still just doing EGFR and ALK. I think we have to expand the targets that we’re testing for.

In this day and age, when we’re doing EGFR testing, most of the time we’re getting those variants by sequencing methods. The most common variants are the exon 19 and 21 mutations, and for the most part, when we’re doing this testing, we’re getting that information. So, requesting a particular type of EGFR mutation, it’s going to be picked up when we do the test. When you order EGFR testing on your patient, you’re going to get the variant on most of the platforms that you test for.

The lesson here is not all EGFR mutations are the same. So, the most common EGFR mutations are the exon 19 and 21 mutations, and those are the mutations that predict sensitivity to tyrosine kinase inhibitors. Those certainly need to be identified before making decisions about up-front therapy with tyrosine kinase inhibitors. But there are other mutations. Certainly, exon 20 mutations are rarer. Those don’t generally predict sensitivity to tyrosine kinase inhibitors, and, generally, chemotherapy is used instead of TKIs. Other rarer mutations in the EGFR gene are captured when we’re doing sequencing, and for those genes, we really don’t know for many of them whether they predict sensitivity or resistance to TKI. I would encourage you, when you get your EGFR sequencing done and you get the test back, that if it is a rare mutation, look it up online to see if this is one that predicts sensitivity to a tyrosine kinase inhibitor. The best data for rare mutations that aren’t 19 or 21 is with afatinib, a second-generation TKI. So, for those rare variants, I will consider afatinib over first-generation TKIs.

EGFR overexpression and EGFR copy number we really don’t use routinely. I think the important point is that we look at the point mutation and the sequencing that’s done to understand and help drive decisions up front. But copy number and expression, those are tests that we really don’t do routinely and should not inform treatment decisions, and should not inform us in terms of a patient’s prognosis.

Transcript Edited for Clarity