Reflex Testing of Next Generation Sequencing (NGS)-Based Panels in NSCLC

EP: 1.Biomarkers and Biomarker Testing in NSCLC

EP: 2.A Commentary on High PD-L1 Expression in NSCLC

EP: 3.Broad Molecular Testing Use in Adenocarcinoma versus Squamous Cell Carcinoma

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EP: 4.Reflex Testing of Next Generation Sequencing (NGS)-Based Panels in NSCLC

EP: 5.Common Biomarker Testing Methodologies Utilized in NSCLC

EP: 6.Case 1: Metastatic NSCLC with an EGFR Exon 20 Insertion

EP: 7.A Pathologist Outlines Typical Tumor Tissue Processing Steps after Biopsy in NSCLC

EP: 8.First- and Second-Line Treatment Options for Patients with mNSCLC and an EGFR Exon 20 Mutation

EP: 9.Considerations for First-Line Treatment Selection for Patients with mNSCLC and Brain Metastases

EP: 10.Repeat Liquid and Tissue Biopsy Practices in mNSCLC

EP: 11.Targeted Therapy Options for EGFR Exon 20-Mutated mNSCLC

EP: 12.Mobocertinib Safety and Efficacy Data in Patients with mNSCLC and an EGFR Exon 20 Mutation

EP: 13.CHRYSALIS Data on Amivantamab and a Comparative Efficacy Analysis of Mobocertinib vs Amivantamab

EP: 14.A Pathologist’s Commentary on The Heterogeneity of EGFR Exon 20 Insertions Found in NSCLC and Considerations for Results Reporting

EP: 15.Molecular Results Interpretation and Subsequent Treatment Selection for EGFR Exon 20 Mutation-Positive mNSCLC

EP: 16.Management of Adverse Events Following Mobocertinib and Strategies for Treatment Modification

EP: 17.Mobocertinib Treatment-Emergent EGFR Mutations and Subsequent Therapy Selection

EP: 18.RET Fusion-Positive mNSCLC: Case 2 Presentation and Molecular Testing Strategies

EP: 19.Selpercatinib and Pralsetinib for RET Fusion-Positive mNSCLC and Supporting Efficacy Data

EP: 20.Occurrence and Management of Selpercatinib- and Pralsetinib-Related AEs in Patients with RET Fusion-Positive mNSCLC

EP: 21.Potential Immunotherapy Use in Patients with mNSCLC and RET Alterations

EP: 22.Looking Towards the Future of Molecular Testing and Additional Treatment Options for Patients with mNSCLC

Joel Neal, MD, PhD: Whose institutions have reflex testing? I know Dr. Shiller you're affiliated with Baylor [University]. Dr. Piotrowska you're with Mass General [Massachusetts General Hospital]. Lauren, you're part of the Sarah Cannon Network. Who's doing reflex testing out there ordered truly by the pathologist and what are the constraints? Is there a histology basis? Is there a stage basis or do the pathologists even look at clinical characteristics like smoking status before deciding? Lauren, you can start us off.

Lauren Welch, MSN, NP-C, AOCNP: Sure, that's the big question. I would say some weeks I would tell you yes there seems to be reflexive broad based NGS testing happening. Because I am also part of Tennessee Oncology, which is a very large community-based practice, some of the patients that we see that get referred in have been diagnosed at other institutions outside of Sarah Cannon and so there is a lot of heterogeneity in how the testing is done upfront if they're not in our hands. I think we do have protocols set up that if we know this is an advanced non-small cell lung cancer, the pathologist is pretty good at sending those tumor samples for next generation sequencing depending on what facility that is. It may be an in-house NGS panel versus externally and so we have some conversations about that and the different kinds of NGS panels that are run. We do have reflex NGS set up, it's not always as consistent as we would like in the medical oncology clinic.

Joel Neal, MD, PhD: What sort of turnarounds do you see for the NGS panels?

Lauren Welch, MSN, NP-C, AOCNP: If it's in-house and they have the tissue right there, we're not trying to acquire it and ship it somewhere, maybe two weeks. When we have our preference and we get to pick an external vendor that has a more complex- it includes RNA, that can be upwards of three weeks sometimes to actually get those results back.

Joel Neal, MD, PhD: Michelle, from your vantage point what are you offering in terms of turnaround times for next gen sequencing panels and what's the panel that you use? We talked in general terms, but every institution has their preferences yet at the same time the clinicians can order something else, a send out that may include other markers for whatever reasons.

S. Michelle Shiller, DO, AP/CP, MGP: So, there are a few layers to your question. First of all, the assay we use we have it labeled as Endeavor, but it was developed through Johns Hopkins and it's FDA cleared. It has 505 genes on it and so like I said we call it Endeavor. It is DNA based. We have the ability to reflex to RNA on as needed basis and we also have FISH and immunohistochemistry and in fact with ALK we can detect ALK by FISH, by immunohistochemistry and by next generation sequencing and RNA. For one particular unique ALK rearrangement we detected where ALK was rearranged with CTLC and there really isn't any data about whether or not that would respond to therapy. We detected that initially on DNA. A provider wanted to make sure that it was real before he moved forward with therapy and so we did simply that. We confirmed it with RNA. We also detected at rearrangement by FISH. It's important to realize that for FISH in that scenario we're just identifying a break apart, we're not necessarily confirming that translocation partner and we did see ALK expression. Like I mentioned early on, it's helpful to have orthogonal methods in particular scenarios so that is how we're using the assay. I love this slide that's on the screen right now about the biomarker targets versus testing methodologies kind of highlighting what I just mentioned. Certainly, there's a potential to miss some things by DNA testing alone and all the different testing methodologies have some advantages and disadvantages. Wanted to also just reiterate that at Baylor [University] there's a pathologist driven reflex standing order; however, the caveat is that that was instrumented through a multi-disciplinary dialog wherein everyone sat around the table. Actually, pathology abstained from voting and all the clinical providers decided this is what they wanted to happen. So, the pathologists do initiate the testing but it's through an agreement that everyone came to. Now in path group because I am part of the path group network, in late January this year I issued a big educational piece about non-small cell lung cancer testing, relevant markers in the space etcetera and made a notification that if you are ordering more than two genes in non-small cell lung cancer that's going to suggest to me that this patient has advanced cancer. There's one FDA approval for a genetic driven biomarker and one for an immunohistochemical. So, I'm going to think that that's what you're looking, and I just can't, knowing the economics of the tissue and tissue storage etcetera, allow that to move forward as single gene testing. We put a notification out there that we will work to convert that to the broad genomic profile. We will call providers if that order comes our way and there may be certain circumstances in which that's needed but we really are trying to pull everything towards that broad genomic profiling in the appropriate clinical setting. Finally, though if we end up not having enough DNA for a broad genomic profile, everyone's loathed QNS results, we do have the ability to reflex to single gene testing and we triage that on a prevalence basis. We always go for KRAS, EGFR, BRAF out of the blocks if we can and hope that we have a slide or two to do ALK gene rearrangement so just some different balances and nuances in looking at the testing in this environment.