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NSCLC: Selecting a Molecular Testing Assay and Interpreting Results
Author(s):
Shared perspective on the armamentarium of molecular testing assays in non–small cell lung cancer and how results can be best interpreted when selecting treatment.
Transcript:
Estelamari Rodriguez, MD, MPH: Dr Levy, what testing methods do you use most frequently? Do you do NGS [next-generation sequencing] or PCR [polymerase chain reaction]?
Benjamin Levy, MD: We’ve come a long way in our diagnostic capabilities. We started with Sanger sequencing, PCR, FISH [fluorescence in situ hybridization], and there’s a simple answer here, and we’ve got good data now. I think you mentioned this before, NGS is the standard of care. I would ask the community to look at what platforms they’re using because some of them aren’t using NGS. When we talk about NGS, we’re talking about DNA testing, as you mentioned, RNA testing. And we know by doing that, we’re not only able to pick up on the point mutations, the insertions, the deletions, but we’re also able to pick up on fusions, as you mentioned, with RNA testing.
We presented data at ASCO [the American Society of Clinical Oncology annual meeting] 2023, a large interrogation of the Flatiron database. It was a poster, and it basically showed for the first time that patients who get NGS are more likely to receive a targeted therapy early and live longer than patients who receive a PCR test. This was the first, albeit retrospective, analysis showing that NGS is better than PCR, at least retrospectively. Now we’ve known that testing vs no testing is important. But I think we need to get away from small panels, and we need to do comprehensive genomic profiling, which is a long way of saying NGS that includes both DNA and RNA. We do the test, the test comes back, and Dr Rodriguez, how do you interpret the results?
Estelamari Rodriguez, MD, MPH: That is a great point because I think, most of us when we went to medical school, who are in practice now, we didn’t get enough, background on how to interpret this test. This information is relatively new, and it’s changing all the time. We do a couple of things. I think the major testing companies for NGS have gotten much better about explaining a test result, and at least adding the companion FDA-approved agent that would be targetable for that mutation you’re identifying. So at least we’re getting some summary information in the front of the report that tells you, of all the mutations we tested—some of these panels are 300, 400 genes—of all the things that we tested, these are the major things you need to concentrate on. Then the more important thing is that the reason we’re doing this test is to find 1 of these 10 actionable mutations that today will change the treatment options. Those need to be up front, and obviously, the reports that do that better are the ones we use because they’re helpful.
We do 2 things. We look at that report, and we’re fortunate enough that we have a molecular tumor board. Sometimes there are mutations there that have a high allele frequency, meaning they’re very predominant and they seem to be involved in that process for that patient. If they don’t fall into those 10 for which we have a clear-cut treatment option, we go to our molecular tumor board for advice in terms of, what is this pathway? Are there any treatment options? And very importantly, some of these mutations there that you’re not acting on can still be used to select clinical trials. There are clinical trials, basket trials that are tumor agnostic. So if you find mutations, and we did this with BRAF, we have done it with RET fusions and NTRK, where you’ve found these changes, and then find a drug that works across many tumor types. We use the results to pick the best treatment for patients. We use the results to pick the right treatment at the right time.
It doesn’t help us, as you mentioned in this abstract, if you do testing after patients have already received chemoimmunotherapy, you may have put a patient on a treatment that was not the most effective. The [tests] need to be done at the right time. So when you meet the patient, I think the hardest thing to do in practice, depending on how long the test takes, is to wait for the results. I will say, today we’re moving faster and better, but still [there are] a lot of frustrations at every institution. We have done this work with the American Cancer Society, [through the] Echo [Project] in Florida, learning from all the institutions in Florida about how long it takes. There’s a lot of variability, a lot of local challenges. I think the send-out test that is a liquid biopsy, we’re getting those back within 7 to 10 days.
The tissue testing is the most challenging today. Most of the big centers send this test out to big companies that have the capacity to do it faster, but they’re not able to run the test until they get good quality tissue. Some of the issues with the turnaround time for the tissue biopsy have to do with tissue acquisition, and the quality of the tissue that is sent, and a lot of delays in the institution getting the test order, finding the test, and sending it out. So I will tell my patients for the liquid biopsy, we will get results in between 7 and 10 days because I know I do the blood test, and I can count on the results. The tissue, we are working hard to get that turnaround to 14 days, but there are cases where there are delays that can take longer. We need to make decisions with the patients in front of us about can we wait for that information before initiating treatment? There are cases where we can’t wait, patients are too symptomatic, and we have started chemotherapy without immunotherapy so that we are able to introduce targeted therapy in a safe way if needed.
Transcript edited for clarity.
