is Tagrisso equally effective on T790M and the original EGFR exon 19 mutation? - 1273499

kempten
Posts:128

Hello
My cancer has a mix of the original EGFR exon 19 mutation , still sensitive to Tarceva;
T790M 0.4 % ; Tp53 R273C 0.2% ; Notch1 E2254K 0.2% ; and FGFR L645L 0.1%

Will any other mutations be sensitive to Tagrisso apart from the T790M mutation?

Thanks
Kempten

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Reply # - April 3, 2016, 04:26 PM

catdander
Posts:

Kempten,

These are the type of questions that are being asked by the researchers. You may get some answers or at least what questions are being asked in trials now by searching the clinicaltrials.gov and other databases from https://www.nlm.nih.gov/

I hope there are many new options by the time you need them.

Janine

Reply # - April 3, 2016, 05:15 PM

kempten
Posts: 128

Thank you Janine,

I just got very confused by some other cancer sufferers interpretations of some of the trial finding.
There is a school of thought out there among some patients that claims, that within the heterogeneous cells in our sub group of lung cancer, only the portion of cells responds well to Tagrisso that exhibit the T790M mutation.
The rest of the cells that still maintain the original EGFR exon 19 mutation , they argue, do not respond as well.
It is said that Tagrisso works best on patients that show the T790M mutation.
So some people have started to imply, that only those cells in your body respond well, and the portion of cells with the original EGFR exon 19 mutation have a less than satisfactory response and will in fact be in danger of progressing again.
This statement totally confused me and I came here for clarification.
I know Tagrisso is being investigated in a first line setting and the above interpretation sounds counterintuitive to me.

Kempten

Reply # - April 3, 2016, 05:38 PM

JimC
Posts: 2753

Hi Kempten,

Third generation EGFR inhibitors such as Tagrisso can successfully treat EGFR mutated cells, whether they bear the initial sensitizing mutations or the T790 mutation associated with resistance to first line EGFR inhibitors such as Tarceva.

That’s why the question has been raised as to whether the third generation agents should be used as first line, a setting for which they are not currently approved. This discussion by Dr. West concludes that although it is feasible, there is no evidence that overall survival improves by doing so. But as far as using these new agents as second line therapy, they may be effective, although it's not clear how effective they will be if the cancer has developed non-T790M-based acquired resistance.

JimC
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Reply # - April 3, 2016, 05:58 PM

kempten
Posts: 128

Thank you Jim,

I'm familiar with the video and listened to it again today.
It was me reading this persons blog post that started to make me question my understanding of the subject
Thanks for reassuring me.

Kempten

Reply # - April 14, 2016, 08:50 AM

carrigallen
Posts: 194

To the best of my knowledge, Tagrisso is just as active for regular EGFR mutations as T790M.

I understand Tagrisso is also active against HER2, HER4, and some less commonly discussed nonreceptor proteins. However, I haven't heard of Tagrisso having activity against FGFR or Notch1. Given T790M presence, it seems reasonable to try.

Reply # - April 14, 2016, 11:36 AM

kempten
Posts: 128

Thank you for the reply.
I got confused about this since some patients have started treating themselves ( through their Physicians of course ) by combining different TKI's to target different mutations within their heterogeneous DNA profile.
When you read the literature, one could get the impression that Tagrisso works best on the cells with the T790M mutation, which if true, would indicate that those patients with a very low allele frequency might not respond as well .
But I also understand that this is all being researched right now.
Thanks again for your reply
Kempten

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