Comprehensive Molecular Testing Needed for Frontline NSCLC Treatment


During a Targeted Oncology™ Case-Based Roundtable™ event, Misako Nagasaka, MD, PhD, held a discussion on the use of biomarker testing in patients with advanced non–small cell lung cancer. This is the first of 2 articles based on this event.


Misako Nagasaka, MD, PhD

Associate Clinical Professor, Division of Hematology/Oncology

University of California, Irvine School of Medicine

Irvine, CA


  • What is the protocol at your center for lung cancer molecular testing?​
  • Which type of assays and gene panels are approved by your center?​
  • Do your assays routinely include EGFR, EGFR exon 20 insertion mutation, ALK, ROS1, BRAF, NTRK1/2/3, METex14 skipping, RET, KRAS? ​
    • Other rarer mutations?​

PAMELA MIEL, MD: In my group, we tend to use Tempus…because Tempus offers a patient assistance program. We do the liquid [biopsy] and next-generation sequencing [NGS] on the tumor sample itself. We test for everything.

MISAKO NAGASAKA, MD, PHD: I think that is an excellent approach. Although I don’t use Tempus, I do both tissue and liquid at the time of diagnosis.

ANITA GUL, MD: It depends on the center where the diagnosis is initially made. They have different preferred labs. I’ve used FoundationOne, as well as Tempus, depending on where the biopsy is done. We ask for the whole panel, PCR [polymerase chain reaction], full sequencing, send out blood and tissue, and also ask for PD-L1 at the same time.

NAGASAKA: I think that’s the most efficient way; do everything upfront using a broad panel. Any other approaches?

WEI BAI, MD: I have been using Caris Life Sciences for tissue only. I sometimes use Guardant360 for the liquid biopsy. I wonder, [since] there are so many companies out there for NGS testing, whether anyone has tried multiple major companies like Caris, FoundationOne, Tempus, [and found] the differences for the genes they test, and also which one is more comprehensive?

NAGASAKA: If we are just looking for the NCCN [National Comprehensive Cancer Network] guideline recommended 8 or 9 genes—the common ones such as EGFR, EGFR exon 20, ALK, ROS1, BRAF, NTRK, MET, RET, and KRAS—I think all of the companies…have the capacity to check for these genes. However, the way of doing the testing may be different with each company, and the panel that they include is different. I’m sure the numbers have changed, but the last time I checked, Guardant Health was able to check for 70 genes, which is more than enough if you’re looking for the 8 or 9 genes that are recommended by NCCN, whereas Caris does something like 650 genes or something [very high]. But in usual practice, as long as you’re using a broad panel, and you are at least including the NCCN guideline recommended 8 or 9 genes, I think it is sufficient. But if you are in an academic center and have clinical trials you can offer to patients for specifically rare alterations—for example, NRG1, [which] is a very rare target that occurs in 0.7% of patients with non–small cell lung cancer [NSCLC]—using a panel that would include those rare genes would make sense.

Is there anyone who does liquid biopsy first, and then if it’s negative, send tissue or the other way around?

MIEL: I do both. But oftentimes I’ll get the liquid biopsy report first, because it takes a while to get the tissue sample from the hospital and then do testing on it.


  • When should molecular testing be repeated for patients with NSCLC?​

NAGASAKA: When should molecular testing be repeated? At the time of progression, [or if there are] not enough tumor samples?

HOWARD YEH, MD: I agree with Dr Miel that the liquid biopsy can be done at the time of the visit, whereas to get the tissue you have to be able to process it. For a hospital to send the sample to Tempus or another vendor will take a while, usually 2 weeks or so. This will be a delay. I agree that liquid biopsy should be done and can be done right away in a clinic. We would have turnaround time in about 2 weeks, and we have the results. At the time of progression is the best time to do liquid biopsy, because the chance of having the circulating cancer cell is the highest. You don’t want to do liquid biopsy when the patient’s already been treated, where there’s probably not much circulating cancer around, and so the yield will be quite low.

NAGASAKA: I agree. I think those are all excellent points. Has anyone canceled their tissue testing because the liquid came back positive? I don’t think you have to cancel tissue testing, but I’ve had times where I thought that maybe the patient can utilize tissue later on for a clinical trial. The patient may have had EGFR or ALK on liquid biopsy, and I use that information to give frontline treatment. I’ve had times where I canceled the tissue testing because the tissue wasn’t even sent to the testing lab. They were still being packaged at the pathology lab.


  • What are some of the non-clinical barriers to testing (e.g., access, insufficient tissue quantity and/or quality)?
  • How often do you receive a PD-L1 report prior to all remaining biomarkers?​

NAGASAKA: How often do we run into barriers?

MIEL: Not infrequently. There are times when you don’t have a tissue sample or there’s insufficient tissue to do testing on.

NAGASAKA: It comes along a lot of quite often because sometimes you don’t have enough tissue, or sometimes it’s in a tricky area that it’s going to be difficult or dangerous to biopsy. So sometimes you can’t do that. When you do have tissue-based molecular testing available, how often do you receive a PD-L1 report upfront prior to the return of all other biomarkers?It might be different, depending on the vendors that you use. If you use Caris, I know that they send that PD-L1 testing report upfront before they send back the whole panel. I don’t know what other vendors do.


  • Do you initiate therapy before all results are returned?​
  • Do you read the entire molecular test report or review specific results?

MYKOLO ONYSHCHENKO, MD: If I need to start treatment soon, I try with platinum doublet and then wait.

NAGASAKA: I think that is fair. There are times when you know the tumor burden is so much, [for instance if] the patient’s already on oxygen and the liver is being replaced by tumor, that you have to start treatment immediately. Yes, in that kind of scenario I think platinum doublet makes a lot of sense.

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