tjv87
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Posts:8
HI,
How common is HER2 amplification with EGFR+ for Exon21 L858R; EGFR amplified, and is there any information that a specific TKI works better than any other for this profile?
Thanks
tjv87
Forums
Reply # - July 19, 2015, 01:08 PM
Hi tjv87,
Hi tjv87,
I will ask to have this question answered by one of our expert faculty. I don't know that there will be an answer but there is good work being done on genomic profiling by places like Foundation One. Have you checked the website? http://foundationone.com/
Janine
Reply # - July 20, 2015, 02:18 PM
Hi Janine,
Hi Janine,
Genomic profiling was done at KEW group. The results showed as above along with a TP-53 mutation. I have read Dr Pinder's articles and viewed Dr. Leena Gandhi's video on the subject but all concur this is a very small sub group. ( HER2 amplification PRIOR to any treatment) so good actionable information is apparently hard to come by.
Here is what I have found so far: HER2 amplification concomitant with EGFR positivity and amplification may confer resistance and early relapse with Erlotinib. Also, HER2 amplification and T790m seem to be mutually exclusive. So this is not the path that the inevitable resistance will take.
We are on Afatinib which is a dual irreversible EGFR and HER2,3,4 blocker.There seems to be some evidence to suggest that this may not be enough by and of itself but at this point so far no one seems to have any ideas as to what might work better.
I'm wondering if more than one inhibitor may be needed at some point and if appropriate dosing of these inhibitors based upon receptor expression pattern in the tumor are needed to overcome this (built in) resistance. If it is even there, because as Dr. Ghandi mentions in her video, HER2 amplification is different than HER2 mutation and it will depend on which of the two; EGFR/HER2 amp, is in the drivers seat at which point during treatment.
We are using Biocept's Liquid Biopsy Lung Profile as a baseline comparative to the KEW results and then following up with monthly tests to monitor CTC and cfDNA trends as well as test for common resistance mutations. My concern is that because our current genomic profile seems to be "uncommon" we might not be utilizing options that could DELAY resistance rather than just finding it when it shows up.
Would one of the Doctors be able to shed some more light on this or correct any wrong conclusions I have made so far?
TJV
Reply # - August 17, 2015, 03:40 PM
TJV
TJV
I'm so sorry your question went so long unanswered. If it happens again please bump up the post to the top of the forum. As you know our specialists have very busy schedules and sometimes miss our requests. I'm usually perfect and this seems to be my first ever mistake. :) Not.
An oncologist should reply soon.
Janine
Reply # - August 17, 2015, 04:29 PM
One problem with HER2
One problem with HER2 amplification is that there is no universal cut-point for positive or negative. The definition varies between studies. Also different studies use different assay methods (FISH, IHC etc).
Using either IHC or FISH assay, HER2 amplification is seen in about 15% of lung cancers, but the importance / relevance of this is still unclear. In some studies, HER2 amplification has been proposed as a route of acquired resistance to EGFR TKI, but this has been controversial.
On the other hand, it is may be associated with better response to EGFR TKIs. See below - this is a study of EGFRm patients treated with Iressa, suggesting that the HER2 gene amplification was a good thing.
http://jco.ascopubs.org/content/23/22/5007.short
In theory, afatinib (Gilotrif) certainly makes sense because it is a EGFR/ HER2 dual inhibitor. Nonetheless, I don't think anyone could be faulted for using another TKI, like gefitinib (Iressa) or erlotinib (Tarceva). I think most of us agree that HER2 mutations are more clinically actionable than the amplifications. So far, HER2 amplifications have limited relevance to clinical care, outside the context of a clinical trial. A randomized trial of Herceptin for HER2 amplification in lung cancer about 15 years ago was negative.