REVIEW article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1599765
Evolution and Targeted Therapy of an EGFR-Mutant Large-Cell Neuroendocrine Carcinoma: A Case Report
Provisionally accepted
- 1Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
- 2Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, GUANGZHOU, China
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We report the case of a 47-year-old female non-smoker diagnosed with stage IV large-cell neuroendocrine carcinoma (LCNEC) of the lung harboring an EGFR exon 21 L858R mutation. The patient exhibited a sustained response to first-line osimertinib, with a progression-free survival of 20 months, followed by transformation to small-cell lung cancer (SCLC) confirmed via histopathological reassessment. Second-line treatment with etoposide and cisplatin combined with radiotherapy resulted in an additional 7 months of disease control. Subsequent progression was accompanied by features suggestive of adenocarcinoma, supported by elevated carcinoembryonic antigen levels, stable neuron-specific enolase, and circulating tumor DNA profiling. Third-line chemotherapy with paclitaxel, carboplatin, and bevacizumab, followed by maintenance therapy with aumolertinib and anlotinib, extended progression-free survival by 21 months. Overall survival reached 48 months. This case highlights the critical importance of repeated molecular profiling and histologic reevaluation in guiding therapeutic decisions for EGFR-mutant LCNEC undergoing phenotypic evolution.
Keywords: Large-cell neuroendocrine carcinoma (LCNEC), EGFR, EGFR exon 21 L858R, TKI (tyrosine kinase inhibitor), lung cancer
Received: 30 Mar 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Li, Li, Yao and Cai. 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: Pengfei Li, 506608785@qq.com
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