Immunotherapy treatment of EGFR/T790M after progression - 1294190

stevenl
Posts:3

Answers to previous posts and other source of information have indicated that "Patients with EGFR do not respond as well to immunotherapy as others. Patients with EGFR should exhaust all other options before trying immunotherapy, including chemotherapy which can be very effective." Does this hold true for patients with high levels (70%) of PDL1 expression?

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catdander
Posts:

Hi Steven,

The data we have shows most people with an EGFR mutation don't have high levels of PD L1 expression. It's thought that the correlation between not doing well on anti pd l1 and EGFR mutation is the lack of pd l1 expression. So I'd not assume the rare lung cancer with both EGFR and PD L1 wouldn't respond to these immunotherapies. If you've got both there's no reason not to try immunotherapies. For most people EGFR inhibitors have fewer side effects, options and are in pill form so there's no need to go into the cancer center for treatment.

All best,
Janine

stevenl
Posts: 3

Thank you for your quick reply. That gives me hope. My wife was diagnosed with stage IV lung cancer almost three years ago. She started on Tarceva, but switched to Tagrisso last spring when the cancer began progressing. The biopsy then came back positive for both T790M and PDL1. The oncologist said that was very rare. She has done well on Tagrisso, but if the cancer progresses again, I was wondering whether immunotherapy was an option. Your answer indicates it might be.

A PET scan this week will give us an update. If it delivers bad news, one question for the oncologist is whether another biopsy will be needed – does mutation leading to progression on Tagrisso change the cell make-up relating to PDL1 status?

A quick thank-you for GRACE and everything that organization does. It has been a wonderful resource these past two and a half years. My wife and I attended the last two conferences and hope to attend many more.

One more request. Can you correct my typographical error in the title of the forum topic? I noticed I misspelled the mutation (should be T790M not T70M).

cards7up
Posts: 636

Do you know what percentage of PDL1? It normally has to be over 50% and preferably even higher.
Take care, Judy

stevenl
Posts: 3

The biopsy last May indicated a score of 70% ("high positive"). One question we will ask the oncologist is whether this value remains stable or might have changed with any further mutation.

catdander
Posts:

It's good to hear that Grace has helped, I can imagine the live patient forums have been very educational. I hope your wife continues to do well with no changes for a long long time. Cancer does change it's make up as a work around anticancer treatment, as it did when it acquired T790M. Too, cancer also will often acquire resistance to targeted therapies such as tagrisso in only one or 2 places while the rest of the body remains under control , for which (as I'm sure you know) local treatment can be used. There isn't any specific information about how tagrisso or it's targeted mutations effect pd-l1 expression since it's rarely seen add that treatment for those with high pd-l1 expression in lung cancer is very new and it's likely to take years before an answer like that could be gleaned. The answer to cancer related questions so often are, "it could happen" and "it depends".
Lung cancer specialists are more apt today to get genetic information (core needle biopsy) at times of progression for several reasons. There are lots of clinical trials testing possible targeted treatments but mostly they'll need fresh biopsy tissue to test for mutations. Those whose cancer has an ALK rearrangement now have several mutations to look for for approved treatments. With the explosion of genetic research, researchers are finding just how much cancer changes with treatment. With my husband’s bad experiences with core needle biopsies that have never gleaned anything diagnosable I would want to try immunotherapy without another and would push to have that ok’d by insurance which may not be a problem at all. I’ll ask a faculty about thoughts on the shelf life of the pd l1 find in a biopsy.

I’m sorry it took so long to answer. I wrote it but didn’t get posted by mistake.

All best,
Janine

catdander
Posts:

Steven,

I did ask and get an answer from Dr. West. But just before starting this post I realized that anyone can get checkpoint inhibitors who have stage IV nsclc and exhausted approved egfr inhibitors. So a biopsy/pd l1 expression wouldn't be necessary anyway, but the high expression leaves immunotherapy a very good option down the road.

Dr. West wrote, "No, there is no standard role for a repeat biopsy to guide treatment after development of acquired resistance on Tagrisso. It's reasonable to try by doing a plasma sample ("liquid biopsy") and/or a tissue biopsy of an area of progressing disease to see whether there MIGHT be a subsequent target to go after, such as a MET mutation or a different EGFR mutation called C797S (which can respond to a first generation EGFR TKI such as Iressa or Tarceva), but that is not required, is not a standard approach, and in fact I have yet to have a patient found to have a useful new result based on a repeat biopsy after developing acquired resistance on Tagrisso."

All best,
Janine