{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:52:48Z","timestamp":1787237568793,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fonc.2025.1599765","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:19:15Z","timestamp":1761542355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Evolution and targeted therapy of an EGFR-mutant large-cell neuroendocrine 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