CASE REPORT article
Front. Oncol.
Sec. Thoracic Oncology
This article is part of the Research TopicInnovative Ways of Targeting the RTK/RAS/RAF PathwayView all 6 articles
Exceptional Response to Furmonertinib in Lung Adenocarcinoma Harboring HER2 Exon 20 Insertion Mutation: A Case Report
Provisionally accepted
- Jinhua Central Hospital, Jinhua, China
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Background: The management of human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) remains a significant clinical challenge, with limited effective and accessible treatment options beyond antibody-drug conjugates such as trastuzumab deruxtecan (T-DXd). Furmonertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with enhanced hydrophobic properties due to its trifluoroethoxy group, has shown activity against EGFR exon 20 insertions (ex20ins) but has not been explored in HER2-mutant NSCLC. Case Description: A 65-year-old male smoker presented with progressive dyspnea and a performance status (PS) of 2. Initial computed tomography (CT) in March 2025 revealed bilateral pneumonic infiltrates. Biopsy confirmed T4N0M1 lung adenocarcinoma harboring the "ERBB2 p.Y772_A775dup" mutation. Administration of furmonertinib at a double standard dose of 160 mg/day resulted in symptomatic improvement and early radiological improvement within 5 days. Following chemotherapy and sintilimab failure in August 2025 due to progressive disease, furmonertinib rechallenge at 160 mg/day again induced a response within 5 days, with no grade ≥3 adverse events. Conclusion: This case provides the first clinical evidence of furmonertinib's activity against HER2 ex20ins mutations. The structural homology between HER2 p.Y772_A775dup and EGFR exon 20 "near-loop" insertions may facilitate TKI binding. Furmonertinib emerges as a potential, cost-effective oral therapeutic alternative for this patient population, especially when standard therapies are not feasible, warranting further prospective investigation.
Keywords: case report, exon 20 insertion, furmonertinib, HER2, Non-small cell lung cancer
Received: 18 Nov 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Lou, Tu, Zhao and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Saibin Wang
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