Molecular marker tests as of June 2014 - 1264322

biggerten
Posts:83

My wife Lucy was diagnosed with Stage IV adenocarcinoma last fall. T2AN2M1A. EGFR wild type and ALK -. Tumor in right lung 3.8cm, nodes and plueral fluid. After 4 rounds of carboplatin/paclitaxel/avastin, the tumor was 2.7cm, classified as stable (I understand this wasn't sufficient under RECIST to be classified as a partial response). Some lingering nueropathy in her feet - bothersome but not terrible.

She is in the Avastin only arm of ECOG 5508, still stable, another CT scan due in July.High BP, but manageable and some pinkish color at times when blowing her nose.

In the meantime, I've been trying to get educated as fast as possible. Trying not to get too excited, but anxiously read what I can particularly the PD-1 and PD-L1 drugs, Nivolumab, Pembrolizumab, MPDL3280A and MEDI4736. Read the abstracts from ASCO.

OK, now to my area of inquiry. It seems that PD-L1 expression is emerging as a marker of interest, and in fact testing is required for participation in some studies. This may require another sample be taken. If we're going to go through that, what additional testing should we be interested in?

Should ROS1 be looked at even though she was ALK-?
BRAF?
MET?
PI3K?
HER2?
Others?

Any other pathway testing - CD27, CD47, etc?

In general, looking for direction for testing beyond what might be standard of care, but still within reason, to avoid additional biopsy procedures.

All this is pending the Avastin maintenance, she's tolerating it well and I see no sense in not riding a winning horse. After that,we'll need to decide, and I want to be prepared.

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JimC
Posts: 2753

Hi Tom,

Probably the main concern about testing for many mutations from a repeat biopsy would be the risk of depleting the sample tissue, which might be necessary for entry into a trial targeting a marker for which you didn't test. For some trials, the test result need not be from currently obtained tissue, so you might want some in storage for later use. On the other hand, if a particular trial requires very recent test results and your broad panel is considered too old for their purposes, you would need a new biopsy anyway.

I think my conclusion would be that at the point when you need a biopsy/change of treatment (hopefully a long way down the road!), choose those markers for which new targeted therapies have been approved or trials of interest are currently available or expected to open soon, banking the rest of the tissue for possible later use.

JimC
Forum moderator

Dr West
Posts: 4735

This is a very rapidly evolving field and question, so I think the "best" answer to this question is very subject to interpretation and changes over time.

I think ROS1 is a real potential "driver mutation" worth testing for if there's enough tissue, and all of the other markers are less established but reasonable to test for. My view at this time is that if there are a bunch of potentially useful markers, it's now possible to send for genomic testing and get results for dozens to hundreds of markers all at once, which would cover all of these and more (the problem being that it's also likely that the results that will come back will include many results that we don't know what to do with). But if you're thinking of looking for more than 2-3 markers, I think it makes sense to test for every conceivable marker at once.

-Dr. West