ALK rearrangement and EGFR mutation in same patient - 1257614

Sat, 06/29/2013 - 07:33

We recently found out mom has both mutations, which her onc said was very rare. She is one month in on Tarceva and we're thinking things are moving positively. Can anyone speak to having both mutations and what the plan of action might be? Tarceva til it stops and then use Xalkori; or use them both at the same time. Or drop Tarceva and move to Xalkori which seems to be more easily tolerated?

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That's good news that your mom has both mutations, making her a good candidate for each drug. Since having both mutations is so rare, it really can't be said that there is a standard way to proceed in this situation. But in general, you usually don't want to use up your options too quickly, so you want to get the maximum benefit from each drug. And since the combination is so rare, there is insufficient evidence whether the two drugs interact negatively.

Until your mom has a follow-up scan, there's no way to know whether Tarceva is effective for her. Once she has that scan, if Tarceva is effective her doctor would likely want to continue it. If not, then Xalkori would certainly be the leading candidate for the next treatment. It's also possible she may show a mixed response, in which some areas of cancer respond while others progress. That's not uncommon, and in this case might be due to some cells being sensitive to Tarceva while others are not. Those progressing cells might be sensitive to Xalkori.

I hope that Tarceva is effective for her and that she doesn't face a treatment change decision for a very long time.

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dr. weiss

I must say that I've never seen a patient with both EGFR and ALK. It is possible that the cells have both mutations, but also possible that some cells have one while others have the other. Some patients with EGFR mutation have dramatic, rapid responses to tarceva that let them know early that it's working--I've seen horrible shortness of breath and pain resolve in just days in people with mutation. My general philosophy is to not stop a treatment that's working. If there aren't too many side effects and scans show that a treatment is controlling cancer growth, I usually continue it. When tarceva stops working in a patient with EGFR and ALK, trying xalkori would certainly be one reasonable option.

Dr West

I think it's important to clarify whether the EGFR mutation is an activating mutation on exon 19 or 21 of the EGFR gene. I actually have seen a couple of patients with both an EGFR mutation and ALK rearrangement, but the last patient I saw with both actually has an exon 20 mutation on the EGFR gene, which isn't associated with a particularly high probability of strong benefit from an EGFR tyrosine kinase inhibitor like Tarceva (erlotinib). Not surprisingly, at least to me, she had previously received Tarceva and progressed right through it, but she had an excellent response to the ALK inhibitor XALKORI (crizotinib).

I'm sure it's possible for a patient to have both an activating (sensitivity-inducing) mutation in EGFR and an ALK rearrangement. There has been no study of such a situation, and it would fall to individual judgment, but I think there would be little enthusiasm for giving both together if a person might respond well to just one of these agents at a time. But the short answer is that there are absolutely no rules and no data to guide a treatment approach in that situation.

Good luck.

-Dr. West


Just wanted to get back to clarify the above questions regarding having both ALK and EGFR mutations. Mom did have 'deletion in exon 19' for EGFR and ALK gene rearrangement. She did not live long enough to try Crizotinib, but was responding very well to Tarceva.