Amivantamab Monotherapy in Rare EGFR-Mutated Advanced NSCLC

Aug 26, 2025

Discover the fascinating case of a patient with advanced non-small cell lung cancer who found success with amivantamab monotherapy, despite struggling with rare EGFR mutations. This discussion highlights the unique challenges of treating EGFR variants and the potential breakthroughs in targeting CNS involvement. Listeners will learn about the implications of this case for future research and treatment strategies in oncology, especially for patients facing limited options.

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INSIGHT

Durable Response In Rare EGFR Mutations

A patient with rare EGFR mutations G719A and A289V achieved a durable response to amivantamab monotherapy after prior therapies failed.
Imaging and ctDNA showed lung tumor shrinkage and undetectable circulating EGFR mutations with CNS disease resolution within six months.

ANECDOTE

Patient Story: Major Functional Recovery

A 67-year-old man with stage IV NSCLC and no smoking history carried EGFR G719A and A289V mutations and progressed on osimertinib, chemo, and immunotherapy.
After starting amivantamab monotherapy he regained mobility and remained disease-stable at 19 months follow-up.

INSIGHT

Unexpected CNS Activity Of Amivantamab

Amivantamab, an EGFR–MET bispecific antibody, showed activity as a single agent against rare mutations and CNS disease in this case.
The result suggests possible blood–brain barrier penetration uncommon for antibody therapies.

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Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. While the development of targeted therapies has improved outcomes for many patients with EGFR-mutated NSCLC, those with rare EGFR variants often face limited treatment options, especially when the disease involves the central nervous system (CNS). A recent research paper, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib” published in Volume 16 of Oncotarget, describes a patient with NSCLC harboring two uncommon EGFR mutations—G719A and A289V—who experienced a prolonged and clinically significant response to amivantamab monotherapy, after prior treatments had failed. Full blog - https://www.oncotarget.org/2025/08/26/amivantamab-monotherapy-in-rare-egfr-mutated-advanced-nsclc/ Paper DOI - https://doi.org/10.18632/oncotarget.28730 Correspondence to - Young Kwang Chae - young.chae@northwestern.edu Video short - https://www.youtube.com/watch?v=UEiCz834a8c Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28730 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal disease About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM