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
Year: 2025
Type: article
Study design: Case Report
Abstract: // Jinah Kim 1 , Liam Il-Young Chung 2 , Horyun Choi 3 , Yoonhee Choi 4 , Maria Jose Aguilera Chuchuca 2 , Youjin Oh 5 and Young Kwang Chae 2 1 University of Vermont Medical Center, Burlington, VT 05401, USA 2 Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 3 The Queen’s Medical Center, Honolulu, HI 96813, USA 4 NIH, Bethesda, MD 20894, USA 5 John H. Stroger, Jr. Hospital of Cook County, Chicago, IL 60612, USA Correspondence to: Young Kwang Chae, email: [email protected] Keywords: amivantamab; monotherapy; rare EGFR mutation; NSCLC; leptomeningeal disease Received: September 04, 2024 Accepted: April 28, 2025 Published: May 29, 2025 Copyright: © 2025 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Patients with NSCLC harboring uncommon EGFR mutations have limited therapeutic options and often poor outcomes, especially following progression on standard EGFR tyrosine kinase inhibitors (TKIs). Amivantamab, an anti-EGFR/MET bispecific antibody, shows efficacy in EGFR-mutated NSCLC, but its role in rare EGFR alterations and CNS involvement, including leptomeningeal disease (LMD), remains insufficiently characterized. We report a 67-year-old male with stage IVB NSCLC harboring EGFR G719A and A289V mutations who developed LMD while on osimertinib. After progression on immunotherapy and chemotherapy, amivantamab monotherapy was initiated. Treatment produced a durable response over 19 months, including a 32.2% reduction in tumor size at six weeks, and complete resolution of brain metastases and LMD by six months. Circulating tumor DNA analyses showed EGFR variant allele fractions decreasing from 25.6% to undetectable. This case challenges current paradigms, demonstrating that amivantamab monotherapy can effectively target rare EGFR mutations, achieve durable extracranial and CNS disease control, and potentially overcome blood-brain barrier limitations. These findings suggest that amivantamab’s utility may extend beyond established combination regimens and well-characterized EGFR mutations, offering an effective option for patients with atypical molecular profiles who lack standard therapies. Amivantamab monotherapy may represent a viable strategy for patients with uncommon EGFR mutations and CNS involvement, including LMD. Further research is warranted to elucidate underlying mechanisms, refine treatment strategies, and assess amivantamab’s broader applicability in similarly challenging NSCLC scenarios.
Source: Oncotarget
Authors: Jinah Kim, Liam Il-Young Chung, Horyun Choi, Yoonhee Choi, Maria Jose Aguilera Chuchuca, Youjin Oh, Young Kwang Chae
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4410860245