CASE REPORT article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
This article is part of the Research TopicMolecular Mechanisms and Innovative Therapies for Advancing Cancer TreatmentView all 6 articles
Germ-line exon 21 EGFR V831H mutation in advanced NSCLC resistance to Almonertinib : a case report
Provisionally accepted
- 1Cancer Center, Lishui Central Hospital, Lishui, China
- 2Lishui Central Hospital, Lishui, China
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Background: Germ-line EGFR mutations are rare, and their clinical significance, particularly regarding response to tyrosine kinase inhibitors (TKIs), remains poorly defined. The EGFR V831H (also known as R831H) mutation is an exceptionally rare variant with constitutive activity, and data on its therapeutic sensitivity are scarce. Methods: We present a detailed case report of a patient with advanced non-small cell lung cancer (NSCLC) harboring a germ-line EGFR V831H mutation. Diagnosis involved imaging, histopathology, and comprehensive genomic profiling of tumor tissue. Germ-line origin was confirmed via Sanger sequencing of normal patient tissue and a familial sample. Case Presentation: A 68-year-old man was diagnosed with stage IIIB lung adenocarcinoma and concurrent latent tuberculosis infection (LTBI). Next-generation sequencing of a lymph node biopsy revealed co-occurring somatic KRAS G12V and an EGFR exon 21 V831H mutation, which was subsequently identified as a germ-line variant. The patient initiated antituberculosis therapy (rifampicin and isoniazid) followed by the third-generation EGFR-TKI almonertinib (110 mg/day). Results: The disease demonstrated primary resistance to almonertinib, with radiological progression in thoracic lymph nodes observed within 20 days of treatment initiation. The patient died one month later with evidence of new brain metastases. Conclusion: This case highlights primary resistance to the third-generation EGFR-TKI almonertinib in a patient with NSCLC harboring a germ-line EGFR V831H mutation. The rapid progression suggests that this specific germ-line variant may confer inherent TKI resistance, potentially exacerbated by the presence of a concurrent KRAS G12V mutation and drug-drug interactions between almonertinib and antituberculosis medications. It underscores the clinical challenge of germ-line EGFR mutations and emphasizes the need for further research to establish effective therapeutic strategies for such rare genotypes.
Keywords: Almonertinib, case report, EGFR V831H, NSCLC, Resistance
Received: 02 Dec 2025; Accepted: 07 Jan 2026.
Copyright: © 2026 Lou, Cai, Zhu 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: Yonghui' Wang
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