EGFR mutation, Immunotherapy, and PD-1 expression - 1271421

Hi advocator, Hope you're alright.

These are still questions that don't have answers, however it appears that pd-l1 expression is higher in those with probable multiple mutations such as people who've smoked while those who have EGFR mutations usually have little or no smoking history and just the one (EGFR) mutation.

Dr. West wrote a blog post on the differences among the immunotherapies. In it he talks about how the lack of expression of pd-l1 isn't as much a predictor of benefit as tarceva is to non egfr mutants. In other words very much worth a try.
"In the meantime, if I’m not blown away by the favorable results with Keytruda, they do show for the first time that PD-L1 expression can be of some value. Importantly, though, the positive predictive value (if you have the marker, you’re especially likely to benefit) and negative predictive value (if you don’t have the marker, you won’t benefit) are less stark than with the biomarkers we’ve readily adopted, like EGFR mutation or ALK rearrangements (though we haven’t really tested ALK inhibitors in ALK-negative patients to any meaningful extent)." http://cancergrace.org/lung/2015/04/19/the-immunotherapy-cola-wars/

Janine

There is ongoing research to answer the question of pd-l1 expression. In there conclusion one group recently noted, "Expression is dynamic in a subset of pts with changes in PD-L1 expression and immune infiltrates observed over time and/or following treatment." http://hwmaint.meeting.ascopubs.org/cgi/content/abstract/33/15_suppl/80…

Thanks for the update and citation - another weapon in the arsenal!

JimC
Forum moderator

Hi advocator,

I wanted to share this with you and anyone else who comes across this post looking for info on pd-l1 expression. This is such a timely subject that new data is still coming in and thoughts change with it. Dr. West wrote this a couple of days ago, http://cancergrace.org/lung/2015/10/10/value-of-pdl1-testing/

All best,
Janine

Hi wadvocator,

What it means is that for some patients the level of PD-L1 expression changes from one point in time to another, sometimes after treatment. So the result you get from expression testing may vary, based on when you test.

JimC
Forum moderator

Is there any literature that shows that Immunotherapy actually doesn't work if a patient is EGFR+, or is it simply that we don't know? I can't seem to find this anywhere, apologies if I have been looking in the wrong place.

Hi gomp,

From the early data, it appears that immunotherapies are not as effective for patients who have driver mutations such as EGFR. Response rates for first line treatment with immunotherapies for such patients are low, but there are ongoing trials testing the efficacy of a combination of an EGFR inhibitor and an immunotherapy agent. This subject is discussed in a GRACE podcast here.

JimC
Forum moderator

Is there anything new on studies that have been looking at a combination of TKI-inhibitors and an immunotherapy agent for EGFR + cancer on exon 19. In addition, I am told that brain mets have been excluded from a lot of these trials. Is that true or can they be stable brain mets?

Thanks

Hi nt99,

The quick answer is here is a video discussion on the subject, I've not watch it but am going to right now. http://cancergrace.org/lung/category/lung-cancer/core-concepts/immunoth…

Brain mets aren't an automatic exclusion into a clinical trial. If they are controlled it is often allowed however each trial is different with is own set of inclusion and exclusion criteria.

All best,
Janine

I just watched the video and see it doesn't contain info you wanted. So I'll say the clinical research being done with immunotherapies and TKIs is too young to say whether it is beneficial or maybe detramental and is being used only in a trial setting.

Hi there. I also have another question regarding EGFR mutations and chemotherapy. My mom who is 67 has EGFR on exon 19 adenocarcinoma stage 4. She had numerous brain mets and there was initially question of early leptomeningeal disease so through the guidance of NIH, she was given Tagrisso 160 for about six weeks. It really helped put the brain mets down from more than 20 to just 2 that are now stable and reduced her primary tumor by about 40%. She then develped what was thought to be maybe pneumonia maybe pneumonitis. It cleared quickly after she was given antibiotics and taken off of Tagrisso. She was then placed on Tarceva but unfortunately, the tumor progressed rapidly in the right hilum ( area of infiltrate that they are calling lymphangitic spread) and pleura but the primary tumor showed reduction and much lower activity. They now want to give her chemotherapy with carbo/alimta and they sent the pleural fluid cells for mutation analysis. The mutation analysis is pending but it showed adenocarcinoma still in the pleura. No small cell transformation noted. My question is , does chemotherapy help with EGFR and since there was some response still in the primary tumor, would it be wise to continue TKI-I while on chemotherapy? This has all been since diagnosis since this past April. Very aggressive tumor.

Hi nt99,

I'm very sorry to hear of your mom's progression. In general, patients with EGFR mutations do tend to respond well to standard chemotherapy, and the combination you mention is frequently used. There is some thought that portions of the cancer might still be sensitive to the EGFR TKI, and that it would make sense to continue the TKI and add chemotherapy, but there isn't good evidence that it is helpful. Dr. Riely discusses this question in a GRACE podcast. Dr. Pennell also discusses options after acquired resistance here.

JimC
Forum moderator