Case 1: Metastatic NSCLC with an EGFR Exon 20 Insertion

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

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

EP: 5.Common Biomarker Testing Methodologies Utilized in NSCLC

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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: Let's dive into our case so that we can talk about how to put all these testing principles into practice, and then use that for treatment and management. So, imagine a 66-year-old Black woman who presents with shortness of breath, chest pain, fatigue, and 10-pound weight loss over the last few months. Past medical history, not really remarkable for anything. Those patients are never smokers, so never smokers less than a hundred cigarettes in her lifetime. Occasional alcohol use socially. Physical exam fairly unremarkable. ECOG performance status, excellent. Chest x-rays ordered by the primary care physician shows a right lower lobe mass. CTs done after that. CT chest, abdomen, pelvis, which confirms a 4.2-centimeter, right lower lobe mass. Right adrenal metastasis, bilateral mediastinal, and hilar lymphadenopathy. At this point, the patient presumably would've gone to see a medical oncologist or get more diagnostics, which included a PET CT showing all of these nodal areas plus the adrenal metastasis. Brain MRI negative for a metastasis so the stage was T2A and 3M1B. A transbronchial biopsy was performed with interventional pulmonology and stage 4A lung adenocarcinoma was diagnosed. TTF1 positive, PD-L1 of 61% positive, and molecular testing started. I think Lauren, this is the place where we're often stuck with that new diagnosis where we say, what do we need to do and how do we reassure the patient that we can wait for this testing? This patient is not symptomatic. What are sort of the techniques that you use as you're thinking behind the scenes as a clinician to make sure that everything gets done, but also reassuring the patient that we can wait for this?

Lauren Welch, MSN, NP-C, AOCNP: There's a couple of different strategies. Since she's not symptomatic, it makes it a little bit of an easier conversation, I think, to explain the rationale for why we need to continue waiting. In her case, we know that the molecular testing has been ordered, so it's cooking. Part of my job in advance would be to try to figure out where it is in the process so I can have some kind of estimate of when we would have answers. If this was a scenario where maybe the tissue was being sent out and we were concerned that it was going to take a while to come back, in this case, we'd often recommend doing plasma testing that day in the clinic just to get the ball rolling, have something that we know we would get back probably in less than a week. That way we know we could bring her back in a week and have something specific to talk about. PD-L1 expression was high so we would talk about her options for immunotherapy, and we try to break it down. Here there's a lot of what-ifs. We'll see kind of where you fall, but broad strokes, we'll talk about upfront chemo, chemo-IO, IO, and then targeted therapy. I try not to get too granular until we have all the pieces of information. An anecdote and I've shared this before that I find really helpful for patients as they're trying to wrap their minds around why am I waiting for more testing or for more information is to kind of give them an analogy of a road trip because the patient comes for their first visit, and they want to start a treatment yesterday. I'll tell them I'm based in Nashville so I'll say if I told you to go to California, go see Dr Neil, you could get in your car, just head west. Eventually, you'll run into California or you could go home, you could pack a bag, maybe you could look at a map, Google the most direct way to get to California, and actually you'd end up getting there a lot faster if you take the time to strategize your trip, maybe even stop off and have a couple of good meals on the way. I think people can relate to the idea of a road trip. This is going to be a journey that I'm on. I want to get there the most direct way, the most successful route. Avoid those detours that aren't going to benefit me. Most of the time people come around when you're able to explain, we're really just trying to get you the right first treatment, and we have to have all the right information in order to do that.

Joel Neal, MD, PhD: I like that analogy. I'll sometimes use the airline analogies and airplanes and talk about how frustrating it is when you're in the plane sitting in the seat, it's pulled back and you go nowhere and you're just sitting there, somewhere in the middle of the airport waiting to go to taxi and doing nothing. That's the feeling, I think, that these patients have but for weeks and weeks. “Getting started with their journey,” I think that's a great analogy.