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Multiplex Testing for Rare Mutations: What Are the Potential Benefits?

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GRACE Cancer Video Library - Lung

GCVL_LU-B09_Multiplex_Testing_Rare_Mutations_Potential_Benefits

 

Dr. Ross Camidge, University of Colorado, discusses the potential benefits as well as the disadvantages of multiplex mutation testing.

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More and more, when people are doing molecular testing on their tumor, they’re not just getting one test and if it’s negative doing another test — that’s called sequential testing, they’re doing lots of tests at the same time — that’s called multiplex testing. There are certain good things about that and certain things which are less than good.

In terms of good things, if you do a whole bunch of tests at the same time, you don’t have as long a delay. If you test sequentially it may take you a while before you get to the positive and if you want to make a decision on your treatment as soon as possible, it’s good to get all the information upfront. Also because when you do the sequential testing, each individual way of preparing the tissue wastes some; multiplex testing is a more efficient use of the tissue, so it reduces the chance that you’re going to need another repeat biopsy.

There’s a certain health economic advantage when you utilize multiplex testing, it is what’s called a noncumulative increase in cost. So to look for ten mutations doesn’t cost as much as ten times looking for one mutation. Maybe it costs two or three times as much, and you can add on extra tests.

Perhaps one of the reasons why we’re most enthused by this idea of multiplex testing is you’re going to find some of these rarer abnormalities. Not just the ALK and the EGFR, but increasingly, there’s a collection of abnormalities which are actionable, sometimes through licensed drugs which are not yet licensed in lung cancer but licensed in other diseases, sometimes because they’re an entry into a specific clinical trial. Examples that spring to mind in lung cancer include RET rearrangements, ROS1 rearrangements, and BRAF mutations.

I said there were a few things which were not good. Perhaps the biggest thing is there are some companies commercially doing this who perhaps are adding too many unnecessary tests, and by that I mean tests that really haven’t got any proven value and they’re using up your tissue, they’re increasing the expense to your insurance firm. Perhaps the other downside is that sometimes you get such a wealth of data, like a data dump, you don’t quite know which one to take to the bank. You get all of this information, there are multiple different mutations, and many of them are not driving the cancer, they’re what are sometimes called passenger mutations, and sometimes that ability to sift through it is pushed back onto you or your doctor. Sometimes there’s an algorithm that will print out, “oh, you’re eligible for this trial, or that trial” and there the issue is, what is their metric for saying there’s good enough data to say, “yes, you should go travel to go on this clinical trial.” Sometimes they have a pretty low bar to get over.

For me the best thing to do is — yes, multiplex testing is a good idea, there are certain companies which are better at this than others, and when you get that information you can’t just assume that everything in it is a meaningful result and you really have to sit down, hopefully with an oncologist who understands this, to go through it.


GRACE Video

Can Patients Benefit from Broad vs. Focal Genetic Testing?

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WCLC_2015_10_Patients_Benefit_Broad_vs_Focal_Genetic_Testing

 

Drs. Ben Solomon, Leora Horn, & Jack West evaluate the merits of broad genetic testing with a “next generation sequencing” platform compared to selective, limited testing for the most proven driver mutations in patients with advanced NSCLC.

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Dr. West:  One of the bigger questions in the whole management of lung cancer is now whether and how often to do broad genomic testing, or really focal testing for a few clearly actionable mutations like EGFR, ALK rearrangement, ROS1, perhaps others that may emerge. What’s your approach — where do you think that your rank and file community oncologist should be, in terms of using broad genomic testing to find, not only the more common ones, but the rarer ones? Do we have enough rare mutations now to widen the scope of our looking, or are there barriers, whether it’s the turnaround time, or others interpreting the results of various rare rabbit holes to go down, that it make it not ready for prime time? Leora, what do you think?

Dr. Horn:  A lot of academic sites are doing it because we have clinical trials. If we’re talking about practical, you know, what day-to-day, I think that it’s important, at minimum, to do EGFR, ALK, ROS, RET, and even BRAF, because there’s been some promising data. If you can get that all done, and maybe it’s through multiplex testing, or next generation sequencing — the problem is, sometimes these test results come back and you get mutations, you don’t know what to do with them, or there’s nothing available for those patients. So, for a day-to-day, practical, we should do those minimal, actionable mutations. I think it’s always nice to know the additional information, but I don’t think it’s essential in making treatment decisions.

Dr. West:  Ben, what do you think?

Dr. Solomon:  So, I agree — I think what’s essential is that a patient gets the best available treatment. Now, the best available treatment will vary from place to place, and country to country, but currently, in most places around the world, EGFR inhibitors and ALK inhibitors are available, and guidelines from professional societies, such as the College of Pathologists, and ASCO, and IASLC, recommend at a minimum testing for EGFR and ALK, and I think that’s a minimum. Now, I think there’s a good case for adding things like ROS1, because of availability of crizotinib, and with the availability of trials at different molecular targets, I think there is a good reason, in most academic centers at least, to expand the panel to include a larger number of actionable mutations, and I think the eventual place that we’ll get to is where all of these tests get done in one test, and we get a report analogous to a Foundation Medicine report that sums up the actionable mutation.

Dr. West:  Yeah, I think once get beyond three of four, it starts to tip the scale toward just get everything at once. I mean, if we’re moving to a time when HER2 mutations, and MET over amplification, as well as, as you said, BRAF, and others, I mean, there’s RET — the list is getting long enough, and it seems that we’re adding maybe one or two every year or so, that hopefully it will be worth doing a broad panel approach for the majority of patients. But, as you say, it depends on where you are and what your access is.


GRACE Video

Dr. Geoffrey Oxnard on What Molecular Markers to Test for in Advanced NSCLC, and in Whom?

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Dr. Oxnard from Dana Farber Cancer Institute provides his insight on which patients with advanced non-small cell lung cancer he pursues molecular testing for, and which molecular markers are the highest priority.


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