Drs. Ben Solomon, Leora Horn, & Jack West consider how valuable testing for PD-L1 expression is in clinical practice and whether it should be integrated in clinical decision making around immunotherapies.

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Dr. West:  One of the key differences that we’re seeing, is really, the strategy that the different companies take in terms of just different denominators, patient populations, and that some are, like nivolumab, is being largely tested in unselected populations looking at PD-L1 levels, or not looking at PD-L1 levels, while several of the other agents in this space are really being restricted to patients who are PD-L1 positive, and seem to, in most of the trials, have a better probability of long response. Do you see PD-L1, now, as an important biomarker that you would use if it’s not mandated — for instance, say, in the nivolumab patients with non-squamous disease?

Dr. Horn:  So, nivolumab, for first line, they are looking at PD-L1. So, when we’re talking about second or third line, with the squamous data, you know, I think a big part of the issue is, is tissue even available for testing? And if there is, which cut point do you use? We’ve even watched with atezolizumab, that cut points changed from their original phase one data, it was 5-10% and now we’re up to 50% cut point. So, right now the data suggests that you can use nivolumab regardless of PD-L1 status, it’s approved regardless of PD-L1 status, and so, that’s the way we’re doing it now. Our hospital is in the process of setting up PD-L1 testing, but it’s not there yet, and, so, the question is, if you are going to use the drug, which assay are you going to send out for, because there are different assays, and which commercial company are you going to send it to — the PD-L1 is a bit of a mess, and it requires a lot of work for us to sort out what to do.

Dr. West:  So Ben, where do you think we are now, and where are we going to be in a few years with this?

Dr. Solomon:  Yes, so look, I think what’s clear is that PD-L1 does enrich for a group of patients that are more likely to benefit. But I think what’s equally clear is that, if a patient is PD-L1 negative, there’s still a chance that they can benefit from treatment with a PD-1 or a PD-L1 inhibitor. So, this strategy of using PD-L1 to enrich for a group of patients who might want to, for example, use a PD-1 axis inhibitor for the first line, probably does make sense, but it probably doesn’t make sense to exclude a patient based on PD-L1 negativity, and the issues that Leora raised about which antibody to use, what lab to get the tests done in, what the cutoff is, absolutely — those are completely unresolved, and who is to know whether a PD-L1 result that you get from a private laboratory has any sort of relationship to the very rigorous, robust PD-L1 testing that’s done in the clinical trials.