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Uncommon EGFR Mutations in NSCLC: Future Directions in Care

Closing out their discussion on uncommon EGFR mutations in non–small cell lung cancer, Benjamin Levy, MD, and Estelamari Rodriguez, MD, MPH, consider how the treatment paradigm will continue to evolve.

Transcript:

Benjamin Levy, MD: Dr Rodriguez, we’re going to finish here. I always love stating in lung cancer where we were, where we are, and where we’re going. And it’s fun because we’re going places now. When I started in lung cancer, it was 3 drugs. And we really didn’t know where we were going. We all know now that science is too fascinating that we’re now heading somewhere. So, what is the future here for uncommon EGFR mutations? Are there agents being tested, [are there] trials? Are there challenges that you still see?

Estelamari Rodriguez, MD, MPH: [T]hinking more about what just happened with EGFR [exon] 20 insertions…we have learned to bypass these difficult-to-treat mutations with the current agents with…better TKIs that understand the structure. So, we saw that in EGFR [exon] 20 insertions, we have mobocertinib as a new option for those patients. We have amivantamab. That is a different drug. It’s an intravenous drug. We’re used to using pills, but an intravenous drug that targets MET and EGFR as an antibody. So, we are finding ways to target the receptor in different ways. Seeing the evolution of EGFR [exon] 20 insertion gives me a lot of hope for what we will have coming forward for uncommon mutations with antibodies. Patritumab, which is anti-HER3, has a possibility of really targeting the receptor in a different way that is not dependent on the pocket, as I say. I don’t know what trials you have seen that you are interested in. A lot of it is early, but we have seen data for some drugs that we thought will be helpful, like poziotinib, that cause a lot of toxicity. We’re looking forward to drugs like BLU-451, which are better. I call them very designed drugs for EGFR. This company has really done a great job of understanding the structure, understanding the CNS [central nervous system] barrier, and finding better drugs for all our patients. All that benefits our patients with uncommon mutations. So those are some of the drugs I’m watching. We’re all watching antibody-drug conjugates. But I have been seeing great data for EGFR. We’re seeing antibodies to the receptor. We’re seeing more selective TKIs in the future that will open better options for our patients.

Benjamin Levy, MD: I think we’re just beginning to scratch the surface like we are with a lot of genotypes. We’re just at the beginning here. We’re in the dark ages still, which is fun, because I’m going to be in this field for another 15 years, I hope. And it’s great to see what’s going to come down the pike. Who would’ve [thought] 20 years ago, 15 years ago, that lung cancer would be the poster child for precision medicine? So, it’s an exciting time to be in the field.

Estelamari Rodriguez, MD, MPH: I think the other thing I’m excited about is the idea of combining drugs, combining the best of one TKI with the best of a monoclonal antibody to really find patients [who] will benefit because their mutations are different. So, I think you're right. And the science is moving fast. It’s what I tell our patients. This is moving fast. This is why we must encourage our patients with atypical mutations, and uncommon mutations, to join trials, because if we don’t collect data on these new agents in their group, we’re not going to learn how to use these drugs. So, encourage [patients] to join clinical trials, to really seek out opinions, and look into ClinicalTrials.gov for their mutation and what options are available.

Benjamin Levy, MD: Amazing discussion. I learned a lot. Thank you, Dr.

Estelamari Rodriguez, MD, MPH: Thank you very much. Great seeing you.

Transcript edited for clarity.

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