What is the Role of Molecular Testing in Resectable Non–Small Cell Lung Cancer?

Shared insight from key opinion leaders on the value of molecular testing in patients with resectable non–small cell lung cancer and how it can be applied.


Balazs Halmos, MD, MS: This patient came to Martin from rural Florida, and the biopsy wasn’t sufficient for any type of testing. What do you do in such a case?

Martin Dietrich, MD, PhD: It is a very challenging situation when we think about the trial design of CheckMate 816 [NCT02998528]. We compared neoadjuvant chemotherapy [with] neoadjuvant chemotherapy IO [immunotherapy]. It helps us to use something very powerful as stand-alone data. The intervention arm was so strong that it was very convincing. But how much response do we actually expect from chemotherapy? Is 3 or 4 cycles enough? How do we approach follow-up care?

When you have a patient who has a pathological complete response, this may not be as difficult…but you do want to know what their molecular [profile is]. In this case, it may be necessary to get a repeat biopsy. I have not been very successful getting enough circulating tumor DNA [ctDNA] from liquid biopsies and early-stage disease. The question is, what are you going to do with [a patient] once they’ve had surgery and a pathological complete response?

The other question is, how do you guide patients for prognostication? Melanoma [research] is always spearheading these efforts for our novel immunotherapy approaches, showing that the intact tumor microenvironment really supersedes the resected tumor specimen and adjuvant immunotherapy. I think it is going to come out the same way in lung cancer.

How do you guide a patient prognostically if you have a squamous PD-L1 negative [result]? The expectation is very different than when you have a KRAS-mutant PD-L1 90% adenocarcinoma. Molecular testing is now at the stage where we should use it across all stages of lung cancer, from stage I through stage IV, to guide therapy selection and therapy treatment. I would not want to give neoadjuvant immunotherapy to an EGFR-mutant patient. We’re going to give an outpatient neoadjuvant immunotherapy. It is very important to have this up front. It makes it more challenging in the multidisciplinary team to get the surgeons to be on board with the idea of getting tumor tissue. Especially for tumors in ... distribution, where no lymph node disease is positive in tissue procurement, it can be particularly difficult. In my book, it has to be done for every patient who requires systemic therapy. It poses the same challenge that we had in stage IV disease. We have to really get good about doing biopsies and selecting good biopsy approaches for patients to guide their therapy the best way possible.

Balazs Halmos, MD, MS: I saw that Kristen was shaking her head when ctDNA was mentioned. What is your team doing at [Johns] Hopkins, in terms of maximizing the tissue and minimizing the turnaround time, patient navigation, tissue stewardship, and things of that nature? What can we do to maximize the potential of that tissue to inform us?

Kristen A. Marrone, MD: We are actively struggling and working on that. We were all getting super excited about next-generation sequencing, adding all these genes, and doing all this great testing. Now we’re headed back to single-gene IHC [immunohistochemistry]-type things. We are [moving] away from super-sensitive things and more toward turnaround time. We are trying to get assays back in 3 to 5 business days, rather than in 10 to 15 business days. I think that has been our biggest issue. There are logistical parts to this problem. What sample is being sent to what lab? What institution? Are you getting a block, are you just getting a few slides? Is that enough? How much tissue did they actually get on a biopsy if the tumor is small or necrotic? Those are all things that we have seen in the past month in our…clinic. Tissue acquisition, testing, and turnaround time are huge unmet needs in the neoadjuvant setting.

Interestingly, all of these studies are doing something different in terms of duration of therapy. There are a lot of unmet needs and unanswered questions that we need to think about in terms of how to operationalize and select options in this scenario, how to use what biomarkers we have, and what we’re trying to look for moving forward.

Balazs Halmos, MD, MS: Certainly, a lot of challenges and a lot of new questions, but also, better outcomes for our patients. I think we’re all embracing that new challenge, in a way.

Transcript edited for clarity.

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