Exon 18 - 1291031

Hi jbarkocy,

Welcome to this side of the forums. We're pleased to know you've benefited from the site. Below I've pasted a link to a couple of videos on the topic of exon 18. In the first video Dr. West begins his discussion of exon 18 at around 10 minutes into the 17 minute video. The take home is that we still don't understand the intricacies of the these mutations and their subsets so you shouldn't rule anything out. In the first video Dr. West discusses data that suggests exon 18 shows efficacy from afatinib and the second video suggests this efficacy may apply to all the egfr TKIs 1st-3rd gen but only afatinib has been studied. We just don't have the answer to this question. In not ruling anything out afatinib deserves to be on the list of next options.
http://cancergrace.org/lung/tag/exon-18/

Chemotherapy and clinical trials are always in the lineup for next options. If you're not being cared for by a lung cancer specialist at a large teaching and research institute you may want to get a 2nd opinion from a lung cancer specialist who knows or can find out of available appropriate trials in your area. And those with an egfr mutation seem to have very good efficacy from chemotherapy with alimta being the chemo of choice for many because of it's low toxicity profile.

Since exon 18 is so rare and its subsets added make knowing about your likelihood to have a t790m mutation unknown. It does "seem" that t790m appears after a durable response to a TKI of around 10 months so your blood test for t790m are likely correct. But again it may be that the test produced a false negative.

I wish there were more certainties but there are more possibilities than just a year ago. Keep us posted on your final plans.

All best,
Janine

Hi jbarkocy,

I am sorry that you did not get a better response to erlotinib. As Janine suggested, given the short period before progression occurred, I think it's more likely that your cancer, and the exon 18 mutation that was found, was not particularly sensitive to the EGFR TKI, rather than that a T790M resistance mutation developed. As Dr. West has said:

"As for predicting what might happen and the exact science of afatinib, I would be very wary about trying to extrapolate results with EGFR TKIs to very rare mutations. Beyond the most common mutations on exons 19 and 21, I think the best answer is that we just don’t know what to expect. Bear in mind that even for patients with an exon 19 or exon 21 mutation, the response rate is 60-70%, not 100%. In general, though, there’s an enormous gulf between the concepts of what an agent does in a lab and what actually happens in the real world.

My perspective is that if someone has a rare mutation, it absolutely makes sense to try an EGFR tyrosine kinase inhibitor in a timely way, especially if they are progressing on chemotherapy or not tolerating it especially well. " - http://cancergrace.org/topic/rare-egfr-p-e709_t710d#post-1258110

And in the same thread:

"I don’t feel at all confident predicting that rare EGFR mutations will respond well, so in such patients, I always want them to get an EGFR inhibitor at some point, preferably in the first couple of lines of therapy, but I don’t feel compelled to rush it as a first line or switch maintenance therapy."

If an EGFR TKI is ineffective, then the first choice would normally be standard chemo agents, or perhaps immunotherapy. Response rates for immunotherapy in EGFR+ patients tend to be low, but that may not necessarily be true in exon 18 patients.

JimC
Forum moderator

I will ask Dr. West if he has any additional comment.

JimC
Forum moderator

Dr. West has this to say:

"I don't know of any data to speak to this and agree with you that the progression likely represents cross-resistance to the available EGFR TKIs. I can't suggest a particular option that I think would be likely to be more effective.

Unfortunately, for rarer EGFR mutations, we just don't have enough clinical data to speak to these questions meaningfully."

JimC
Forum moderator