Potential Immunotherapy Use in Patients with mNSCLC and RET Alterations

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

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

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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: At least in my experience, immunotherapy is not particularly highly active in this case. Have you seen good responses to immunotherapy in RET-positive patients, Zosia, or Lauren?

Zosia Piotrowska, MD: I would say generally no. I think of these as similar to patients with EGFR and ALK, and I think if you look at some of the registries like the IMMUNOTARGET registry, the numbers are small but the responses are limited, so I think you have to use immunotherapy very much with caution in these patients. And like with some other oncogene-driven cancers, really often I will reserve immunotherapy only for a point when we might've exhausted both our standard of care and clinical trial targeted therapy options for these patients. I guess one other thing, Joel, to mention is just that both of these drugs have really good CNS penetration, and I think that's a really important point. And again, it's just so nice when we have these drugs that have good CNS activity in the clinic and I think both pralsetinib and selpercatinib have demonstrated CNS activity, and for patients who present with brain mets are a good choice.

Joel Neal, MD, PhD: Lauren, any thoughts on immunotherapy in this patient population?

Lauren Welch, MSN, NP-C, AOCNP: Yeah, I guess defining what we mean by immunotherapy, I think what we're talking about today is checkpoint inhibitors. And I agree exactly with what Zosia said: We're predominantly saving that for when we've tried everything else that's been exhausted. But we have had some anecdotal successes with some novel IO mechanisms in these kinds of patients, so we're not afraid to, if they've exhausted all of their targeted therapies and chemo, to try some of these new novel IO agents. And sometimes those newer mechanisms are able to work better than standard checkpoint inhibitors.

Joel Neal, MD, PhD: Yes, platinum-based therapy is of course the option, standard option after use of the RET inhibitors. While the platinum and pemetrexed is compelling, I think the addition of anti-angiogenics or even immunotherapy, for lack of anything else, is perfectly reasonable. But not a lot of responses to immunotherapy itself.