Treatment of NSCLC With Uncommon EGFR Mutations - Episode 2
Sarah Goldberg, MD:This patient has anEGFRmutation, so it’s not at all unexpected that she’s wild-type forKRASandALK. In general, we do test for many mutations at the diagnosis of advanced or stage 4 NSCLC, specifically lung adenocarcinoma. And looking forEGFRandALKare 2 of the most important genes to look at because we have targeted therapies that can work very well for those. There are other genes that are very important to look for mutations in, includingRAS1, BRAF. There’s many others.METis actually also an important one.KRASis an interesting one to talk about because we don’t have targeted therapies forKRAS. One important reason to check it might be that typically if there’s a mutation inKRAS, the other ones are usually negative, although sometimes you can see multiple alterations in genes. But typically, if one is positive, the others are negative if they’re mutually exclusive. So, again, in this patient, it’s not surprising that since she does have anEGFRmutation that theALKandKRASare negative.
There are 2 types ofEGFRmutations that are, by far, the most common in NSCLC, specifically lung adenocarcinoma. That’s the exon 19 deletion and the L858R point mutation in exon 21. So, those 2 types of mutations make up, again, the vast majority ofEGFRmutations, probably around 90% of the mutations. When we see a patient with anEGFRmutation, that’s typically what we see. And those 2 types of mutations typically make the cancer very sensitive to EGFR inhibitors. And so, when we find that, it’s usually a very good thing for the patient because we have drugs that can work very, very well for their treatment.
There are several drugs that we have now that are EGFR inhibitors that are options for patients, but those are the common mutationsthat’s what they’re typically called, the commonEGFRmutationsand they are sensitizing as well, meaning they sensitize the cancer to the EGFR inhibitors.
EGFRmutations can be in this rare category, or uncommon category. About 10% of them fall into that category. And this patient has one of them, theG719mutation. There are about 10% ofEGFRmutations that fall into uncommon category. And what’s important to note about the uncommonEGFRmutation is that some of them still are sensitizing. So, uncommon doesn’t necessarily mean that the drugs won’t work, the EGFR inhibitors won’t work. Uncommon can be sensitizing to the drug, and that’s the case with this patient’s mutation. This is the type of mutation that is uncommon; it’s rare inEGFRbut still can make the cancer sensitive to the EGFR inhibitors.
Transcript edited for clarity.