Metastatic Adenocarcinoma of the Lung - Episode 4
Transcript:Mark A. Socinski, MD: Let’s talk about the future. How are things going to be 5, 6, 7 years from now? Will it be any different than they are now? Will we be testing any differently? Will things be cheaper, quicker, faster, greater return on our investments?
Gregory J. Riely, MD, PhD: I think I’ve become much more realistic in my expectations of what the 5-to-10-year timeframe brings, and my guess is that in 5 years, we will be routinely getting enough tissue at the time of diagnosis to allow us to do the tests we want. Not knowing for sure the landscape of things, but my presumption would be that you guys are reflexively going to be doing PD-L1/IHC on every lung cancer specimen that walks through the door. That’s going to be a key standard first-line drug. It’s going to be necessary to know that information up front. Which antibody are you using? I’m not sure about yet. And, as Mark alluded to, the BluePrint project is really going to help us with that.
Mark A. Socinski, MD: Yeah, just so people understand: the International Association for the Study of Lung Cancer, or IASLC, has all the four major companies’ antibodies that are in this space. They’re doing a prospective study on a set of 40 cases to try to work out the IHC, hopefully to get to a point where we have one standard test rather than four different antibodies, the two approved, and maybe other ones down the road. John, one question. I thought of this when Greg was just speaking. Why do a biopsy? Why not just draw the blood, get everything you want?
John W. Longshore, PhD: Great question. We haven’t even talked about so-called liquid biopsies, and I was hoping that we would get there, because particularly in the community setting, I like to say not everyone has access to specialized biopsy collection procedures. But I bet everybody has a good phlebotomist. So plasma-based testing is something that is hopefully very near to approval in the US. It’s already approved in the European market.
The issue we have with plasma-based testing for biomarkers at present, for instance EGFR, is with our current technologies—either real-time PCR or next-generation sequencing. It’s not quite as sensitive or specific as you see with a tissue-based diagnostic. So, what many institutions are starting to do as they move into plasma-based testing for circulating tumor DNA, is to use the plasma-based testing as a first-line. And if you get a negative result, realize that the sensitivity is going to be much better with tissue and then maybe go to tissue. If you do find a mutation with a liquid biopsy, it is certainly understandable to move forward with therapeutic decisions based upon that result.
Mark A. Socinski, MD: You mentioned cell-free DNA. What about circulating tumor cells?
John W. Longshore, PhD: Circulating tumor cells are something that we have had available in the US for many, many years. But it seems that more of the current work is being done with circulating tumor DNA rather than circulating tumor cells. The nice thing about circulating tumor DNA is it is much easier to isolate from plasma versus a circulating tumor cell isolation having to be done at a very specialized medical center.
Mark A. Socinski, MD: Greg, your perspective?
Gregory J. Riely, MD, PhD: I’m excited about liquid biopsies, circulating tumor DNA. This is clearly the way of the future. But what I’m really cautious about is, what’s in clinic today? What’s being sold to the average oncologist today? Relatively little validation has been done for those sorts of things, and as you suggest, we can’t really believe a negative result. We have to go further, so I think it’s really important to take all this information that we’re getting now with a grain of salt and look forward to validated tests being in clinic.
Mark A. Socinski, MD: But because oncologists are hearing a lot about blood-based testing, and are seeing people in their office that are promoting it at this point, a lot of it’s been done. We’ve used it with a lot of our patients. The great example that John brought up, the T790M mutation, we’ve made several diagnoses and have been able to get third-generation drugs on the basis of blood testing. Ben?
Benjamin P. Levy, MD: I just want to add to what Greg said, which I think is important. Nobody's more excited than I am about plasma genotyping. And there is potential to circumvent tissue biopsies altogether, given the hurdles that are associated with tissue biopsies. But there are different competing platforms coming out each day that are looking at cell-free DNA specifically, and they all have different sensitivities, or reported different sensitivities, specificities, and concordance rates. Without a lack of validation and standardization, I think we have to be careful moving forward. We need those prospective trials that mandate plasma and/or serum, and compare it to tissue to get good concordance rates and understand the predictive value. I’m using plasma genotyping right now with many of my patients, and I have found it nice to have this test up front, given that their specificities are quite high, sensitivities are a little bit low. But I think this is where we’re heading. We just need to have those validated prospective tests, prospective studies that we can get an understanding of the real predictive utility.
Thomas E. Stinchcombe, MD: I’ve used some of this blood-based testing. One of the hazards is you get the test, it’s negative, then you don’t know if that’s a false negative and then you have to do a biopsy. And this does incur a delay in terms of transitioning the patient from one therapy to another.
Mark A. Socinski, MD: That brings up a good point. What should be the community oncologist’s expectation of how long it takes to get this testing done from a lab-based point of view?
John W. Longshore, PhD: Right. Well, the latest guidelines we have from CAP/AMP and IASLC are about two years old.
Mark A. Socinski, MD: No, we don’t like when it says two weeks. We need it quicker.
John W. Longshore, PhD: The goal is five working days, but two weeks is given largely to accommodate the community setting where you don’t have testing in-house and you’re having to send out to a reference lab. But certainly quicker is better. In my own institution, we have our biomarker testing for EGFR, BRAF, and KRAS done in about a two-day turnaround time. So it can be done if you have the appropriate platform and the appropriate laboratory support to do that.
Thomas E. Stinchcombe, MD: I have to be candid. We struggle with the two-week deadline at times. It’s still an admirable goal.
Mark A. Socinski, MD: We don’t always get ours within two weeks, but usually by two-and-a-half weeks or so, it’s usually there. It would be nice because patients are waiting. That’s why we’ve been able to use the blood test in lieu of that and get an answer quicker with some of these blood-based tests.
John W. Longshore, PhD: That would be another great advantage of reflexively ordering. When the biopsy is done, the biomarker tests are reflexively ordered because the diagnosis has already been made.
Jared Weiss, MD: And I think if we’re going to be candid about the real world, then we ought to admit that there’s a lot of non-testing going on in our country.
Mark A. Socinski, MD: Because of tissue issues.
Jared Weiss, MD: Tissue is one of the big reasons that my community partners will cite as a reason. They’ll say in XYZ location that it’s much harder to get a biopsy. I can’t get a next-day biopsy or something the way you can. And this is exciting to me because it could potentially help address that.
Mark A. Socinski, MD: Right. And the other thing we should say before leaving this session is that we should be thinking at the community level about how to do that initial biopsy, because we see so many patients that come to us for a second opinion or, I like to say, the best opinion. And they had a bronchoscopy with a wash. They know they have cancer but there’s little to work with, and rather than the conversation starting off, “This is how you should be treated,” it’s, “Let’s talk about getting another biopsy so we can know what we need to know about your diagnosis.”
Transcript Edited for Clarity