2 mutations? - 1268757

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bigbill
2 mutations? - 1268757

I have been advised by my doctor that I am fairly unique in that I have both the EGFR(exon 19 deletion) and PDL-1 mutations. I am a 50yr old WM stage 4 nsclc never smoker and am starting on the first line tarceva+ avastin treatment. Wondering if anyone else out there has both mutations? haven't read anywhere about the discussion of someone having both gene mutations.-Bill

catdander
Hi Bill, Welcome to Grace.

Hi Bill, Welcome to Grace.

I hope you do really well the combo for a long long time.
It's true that having 2 mutations is rare but it definitely happens. If you're going to find others with 2 mutations or 2 of the same mutations it will most likely be on social media or public forums like this. There are also longevity and inspire among other forums where you can also ask. A thought is if you find others and want to start a continuing thread or 2 you we encourage you to start threads in our Patient/User Groups forum, http://cancergrace.org/forum/lung-thoracic-cancer/patientuser-groups You never know what a few rare outliers may have in common that no one has noticed before.

Please keep us up to date on your treatment and let us know of any questions that come up.

Janine

wadvocator
I know that EGFR is a

I know that EGFR is a mutation. Is PD-L1 a mutation?

JimC
No, it's a protein over

No, it's a protein over-expression. As Dr. Pennell explained:

"PD-L1 is a protein on tumor cells and tumor stroma (the normal non-cancerous tissue in a tumor) that binds to PD-1 on immune cells and causes the immune system to turn off, allowing the tumor to escape destruction by the immune system. The drugs targeting PD-1 and PD-L1 interfere with this process. The idea behind looking for the presence of PD-L1 in the tumor is that blocking this system seems to be more effective when the PD-L1 is there. Perhaps if it isn’t there then the PD-1/PD-L1 system is not preventing immune attack and giving the drugs won’t do anything.

There are several issues with this assumption. First of all, every company uses a different method to define “PD-L1 positive”, using different antibodies and different cutoffs of what is positive or negative. So theoretically a biopsy could be called “PD-L1 negative” by one test and be called “positive” by another. Second, PD-L1 expression can vary from area to area within a tumor or even in different sites of spread within the body, so any one biopsy may not reflect the whole cancer; i.e. they just may have missed the part that was positive and biopsied a negative area. Finally, PD-L1 expression may change over time and with treatment. If the tissue being tested is from the time of diagnosis and is negative, it is possible that later on after radiation or chemo that a new biopsy could be positive. All of these are hypothetical but this illustrates how little we really know about this biomarker.

We do know that some patients labelled “PD-L1 negative” still do respond to immune checkpoint inhibitors, and my guess when that happens it is for one of the above reasons. Since most trials require PD-L1 to be positive, then the options would be to be tested again using another test (or with another biopsy), or to enter a trial that does not require a positive test." - http://cancergrace.org/topic/medi4736/page/2/#post-1264732

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>