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Can Patients Benefit from Broad vs. Focal Genetic Testing?
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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.

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