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Should PD-L1 Testing Be Ordered at Diagnosis or After Progression?
Thu, 11/12/2015 - 06:00
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Drs. Leora Horn, Ben Solomon, & Jack West consider the factors that might lead us to favor testing for PD-L1 at initial workup of a patient with advanced NSCLC or after progression.


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Dr. West:  What about the timing of PD-L1 testing? We’re used to doing testing for various biomarkers at the time of initial diagnosis, and I think that it may be a barrier if you have a patient who’s progressing now, with multiple new liver lesions and a new adrenal metastasis, to then have to go send them to interventional radiology, wait a few weeks for the result, and potentially not start your second line therapy choice until a month or more later. I think this was a particular issue when they were trying to look at PD-L1 in relapsed small cell, where a lot of the patients were progressing too fast to act on the results. So, is PD-L1 testing likely to be a barrier, particularly in the setting of previously treated, and now progressing, patients?

Dr. Horn:  So, there was data at this meeting suggesting that there’s fairly good concordance between initial diagnosis and testing at the time of — some of these patients were tested for entry on study; I don’t think that is as much a barrier as the initial trials — you couldn’t test pleural effusions, you couldn’t test FNAs, it had to be core biopsies, and many lung cancer patients are diagnosed off an FNA or a pleural effusion…

Dr. West:  FNA being, fine needle aspirate.

Dr. Horn:  Fine needle aspirate, and so, how do you interpret those results? But, if you have an initial biopsy that’s PD-L1 positive, the data seems to suggest that, for the most part, that remains even at the time of progression on chemotherapy.

Dr. West:  That’s certainly important — what’s your sense of this, that it’s, really, early or not bother?

Dr. Solomon:  I think we’re to think about PD-L1 as a biomarker in a different way than we think about EGFR mutations or ALK gene rearrangements. So, EGFR mutations and ALK rearrangements we think of present, right from the beginning, they’re an essential part of the tumor — when we talk about tumor heterogeneity, we describe them as being in the trunk of a branching tree. But, PD-L1 is potentially a dynamic thing, and I think it’s reassuring to see the concordance data that was presented by, I think it was a Genentech group that presented that data, between biopsies taken at different times or at different places in the same patient. But we’ve also seen sections of tumors that have some parts that stain positive for PD-L1, and others that are negative, which does raise concern about how much we can believe one particular result. So, I think it’s, again, an unresolved question.

Dr. West:  Again, early days still, there’s still much more to learn.

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