Navigating Uncommon EGFR Mutations in NSCLC: Challenges and Insights

Transcript:

Charu Aggarwal, MD, MPH: Nagashree [Seetharamu], can you expand on uncommon EGFR mutations and tell us how you differentiate between common and uncommon in clinic?

Nagashree Seetharamu, MD: The word uncommon is a misnomer, I think, and you know, we’re detecting more and more of these. In fact, even the common mutations, as we discussed earlier, there are many of them. The insertions and the actual location of the deletion might be important, so I don’t know what the definition means anymore, but I like the John Heymach [MD, PHD,] classification. I think that’s probably the best use here. But having said that, the mutation spanning from exon 18 through 21, making sure that we have a platform to detect all of that, is important. And to see if this is one of the classical mutations, L958R or exon 19 deletion or exon 20 insertion—that’s a separate class, and everything else falls under the uncommon mutations. I think I’m in the T790M minus.

But everything else falls under the uncommon mutations. I also think patients who have dual mutations fall under uncommon mutations as well. I’m not sure that there’s a clear definition for uncommon mutation, which is not so uncommon. I also wanted to bring up the issue that we’re only talking about EGFR, but there are external factors like p53, we’re not discussing that right now, but you know, p53, RB1, etc, that may be playing a role in how the patient does with individual TKIs [tyrosine kinase inhibitors]. But for definition purposes, I would say anything that is not classical type exon 20 or T790M, I would put in the bucket of uncommon mutations.

Charu Aggarwal, MD, MPH: Are you looking at these mutations, standardly, in your biomarker testing panels, or do you have to request them in addition? I believe you are the one who said that you get EGFR, ALK, and PD-L1 on reflex, so how are these uncommon mutations reported at your institution?

Nagashree Seetharamu, MD: That reflex I mentioned is only for early-stage patients. So if it’s in the neoadjuvant or the adjuvant setting, the EGFR gets reflected out. But for the advanced stage, we do get the full-panel NGS [next-generation sequencing] testing. So we do get the full panel. Do I have to request specifically? No. The gene is read out completely with specific mutations, even when they do single-gene testing. In fact, we send it to Mayo Clinic. They do a full gene panel assay but only single gene for earlier stages. I’m sorry if I was misunderstood.

Charu Aggarwal, MD, MPH: That’s great clarification, and I think it’s just an important point to remember that we should be looking at the entire panel across the spectrum of the EGFR domain to ensure that we are looking for these mutations. Would you say you do this pretty often, or do you do this all the time? What proportion of your patients get full sequencing?

Nagashree Seetharamu, MD: One hundred percent of the time in advanced stage.

Charu Aggarwal, MD, MPH: That’s excellent.

Transcript edited for clarity.