Everett Vokes, MD: As part of immunotherapy, we are looking at PD-L1 testing, and biomarkers, and enriching our patient population. Particularly, for those who have newly diagnosed disease, there are questions about that. Should all patients be tested? And, how do we use the test results to determine frontline therapy? And I know, Fred, you’ve thought a lot about this. You’ve worked in this area for a long time. How would you summarize where we are?

Fred Hirsch, MD, PhD: Thank you Everett. Of course, with the presentation of the results of KEYNOTE-024 last year at The European Society for Medical Oncology 2016 Congress, KEYNOTE-024 was the frontline study of pembrolizumab versus chemotherapy. In that study, the patients were selected by PD-L1 expression using criteria of 50% or more (for expression of PD-L1). This study showed superiority for pembrolizumab in frontline therapy in patients who were EGFR, wild-type ALK, or ROS wild-type.

So, with that there was a shift of paradigm for frontline therapy. And that made, also, in my opinion, PD-L1 testing mandatory for all patients (except those patients in whom you know have an EGFR mutation or an ALK or ROS gene rearrangement). Now, the problem is, in my opinion, it was clearly defined in the pembrolizumab study—the assay with the Clone 22C3 and cutoff level of 50% or more. But, there has been other approved and used assays. As you know, every company has their own assay. They have, also, in their package, specific recommendations for the staining procedure, and the treatment, etcetera. Even cutoff levels are different from study to study. So, it is very clear that for frontline therapy, all patients should be tested (unless they have an EGFR mutation, or ALK or ROS rearrangement), with that specific assay approved for pembrolizumab.

Now, we have second-line studies where pembrolizumab is approved with another cut point. We have complementary assays, which are not required for treatment but are recommended as a guidance for treatment effect. So, the field is a little bit confused on this stage.

IASLC (the International Association for the Study of Lung Cancer) has taken upon the responsibility to work with the companies to compare their assays. That is what we call the Blueprint Project. The first phase of this project has already been completed and published. It showed that 3 out of 4 assays was very similar, while 1 assay, SP142 (which is used for atezolizumab), has a different profile in terms of PD-L1 expression. I think the Blueprint Project is important because we hope that we eventually could harmonize the assays and avoid the confusion out in the community. But, with pembrolizumab approved in first-line therapy based on this assay, the answer is, everyone should be tested.

Naiyer Rizvi, MD: If you have a newly diagnosed patient and you don’t have the right material or enough material for a PD-L1 test, do you send them for another biopsy for a PD-L1 test?

Fred Hirsch, MD, PhD: The scenario currently tells us that you should have a PD-L1 assay for putting the patient on pembrolizumab, for first-line therapy. I know there are certainly places where that doesn’t happen, and I cannot, of course, recommend something which is not approved. So, the short answer to your question is, if you don’t have sufficient material for PD-L1 testing and the patient is negative for an EGFR mutation, or ALK or ROS, then I would recommend to seek a new biopsy.

Everett Vokes, MD: The reason for that is there’s a survival advantage for patients receiving pembrolizumab (at least a progression-free survival). But, also a survival advantage for patients with PD-L1 staining over 50%?

Fred Hirsch, MD, PhD: Right.

Everett Vokes, MD: And so, you don’t want to deprive those patients of that possibility. Is that correct?

Fred Hirsch, MD, PhD: Absolutely.

Transcript Edited for Clarity