Part 2: Biomarker Testing at the Time of Disease Progression

Having considered the basics of biomarker testing, our panelists turn their attention to challenges of biomarker testing at the time of NSCLC progression and share their perspectives on the current NCCN guidelines for biomarker testing and how they might be modified.

This roundtable discussion is sponsored by Daiichi-Sankyo.

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Spoken by Corey Langer, Aaron Lisberg, Lyudmila Bazhenova, and Misako Nagasaka

Transcript

Corey Langer, MD:
So that brings up, again, assessment at the time of progression. I think we've all mutually adopted liquid biopsy, but if a patient’s disease is progressing rapidly, I think in that situation, at least for me, it's imperative we get tissue. We're not going to identify transformation in the liquid biopsy. I assume that’s the same for all 3 of you? Yeah. So you go after at least the site that's probably progressing the quickest, because that's likely to have the greatest yield. NGS is pretty much superseded, anything else? Can you think of any situations where you would not do NGS, IHC, or FISH or older approaches or single-spot testing?

Aaron Lisberg, MD:
Yeah, like I said, at our institution, we still kind of historically have an EGFR test that does come back very quickly. But then, and obviously, if it's positive for sensitizing mutation, that's helpful, but yeah, you have to do the full NGS.

Corey Langer, MD:
Do the NGS and of course, get liquid in that situation, regardless,  which has been a bit of a challenge because we're geared up to do that outpatient, but not necessarily inpatient. That's the one situation where I have done spot testing or single-gene testing; again, concentrating on the most likely ones, EGFR and ALK, and I think we've thrown in ROS. So at least there, we might have a 1-, 2-, 3-day turnaround. We can still do that internally. I did mention that we do everything internally but it’s not quite true; as a double check, at least for the fusions, we do send tissue out to NeoGenomics. So, we're doing separate fusion panel, we're doing internal fusion, but then a double check on the outside panel.

Corey Langer, MD:
I think we've all agreed that we're not deferring liquid to disease progression, but it seems to me that, at least in the community and maybe some academic centers, but certainly in community, that is the general trend.

Corey Langer, MD:
Do you find that things have changed in Southern California where all 3 of you practice or that they're adopting liquid early on, or it's still basically either not being done or being done at the time of progression, Aaron?

Aaron Lisberg, MD:
Yeah, I would say that when I talk with community docs, I'd say it's less common to be sending both tissue and liquid at time of diagnosis and parallel. I think that is a bit unique to the academic community; at least in my region, I think that that's true. But certainly, the value of getting liquid testing at the time of progression is appreciated by all oncologists. I mean, it's much easier to get that, obviously, than to convince a patient to get a biopsy. So I think the liquid biopsy still are being used at a relatively high rate, but I do agree at time of diagnosis I'd see it less.

Lyudmila Bazhenova, MD:
Yeah, I think we see the same pattern. So I see a much more higher use of liquid biopsy post-progression rather than a tissue biopsy post-progression. And I think one important thing we have to highlight is the fact that the liquid biopsy can be false negative. And unfortunately, I still see situations where the only molecular testing for the patient at the time of the diagnosis was a liquid biopsy, and that missed a targetable alteration. And when, let's say, patient came for a second opinion, we realized that tissue was never sent out. We do the tissue biopsy after patient failed first-line therapy, and then sure enough, discover an oncogenic driver that just wasn't visible on the liquid biopsy. And another thing we have to remember that if you are treating patient with oncogenic driver and you are doing a liquid biopsy after progression, liquid biopsy is not able to determine histologic transformation, right? So, you miss all your small-cell transformations because you will not see it on a liquid biopsy. On the other hand, I think it is better to have a liquid biopsy post-progression than to have nothing post-progression on a patient who gets oncogenic driver. And I think it's still important to understand the false negativity rate of the liquid biopsy to make sure that you're not missing potential actionable alteration.

Misako Nagasaka, MD:
Yeah, I would agree to what was mentioned by Lyudmila. So I think in the community, it's quite rare for patients to get both liquid and tissue biopsy up front at the time of diagnosis. But I have seen, unfortunately, patients who had a negative liquid biopsy be treated with the 189 regimen and only later to be found that they have a driver mutation. So that happens, yeah.

Corey Langer, MD:
So if that patient's had disease progression, you will routinely recommend tissue biopsy if they have no prior molecular profile on file.

Misako Nagasaka, MD:
That's correct.

Clinical Practice Guidelines for Biomarker Testing in Advanced/Metastatic Non-Small Cell Lung Cancer

Corey Langer, MD:
Um, thoughts about the NCCN guidelines? Of course liquid's included now, but I don't think we've quite made it standard of practice; obviously, or correct me if I'm wrong, but I don't believe the guidelines specifically state you ideally should do both tissue and liquid. Do you think that should change, Aaron?

Aaron Lisberg, MD:
It's a difficult question. Obviously, the fact that we're all doing that, and I think we have good rationale and I think there's good data to support that, suggests that I do think that is what's best for our patients. Again, there are regional differences in terms of insurance reimbursement, and I know that even getting any testing can be difficult in some settings. So taking from there all the way to, you need to get to maybe a difficult lead, but I do think that's where we will be eventually. And I do think there's good rationale for doing it. So, in the interest of the patient and identifying a target, if it's available, I think the best approach to that is yes: getting both liquid and tissue and parallel time with diagnosis. So, I do think that at some point the guideline should reflect that.