# Case report: A patient with EGFR L861Q positive adenosquamous lung carcinoma transforming into large cell neuroendocrine cancer after treatment with Almonertinib

**Authors:** Kele Cheng, Yong Zhu, Ran Sang, Zhongsheng Kuang, Yang Cao

PMC · DOI: 10.3389/fonc.2025.1453066 · 2025-02-18

## TL;DR

A patient with a specific EGFR mutation in lung cancer developed resistance to Almonertinib and transformed into a different cancer type.

## Contribution

This case report highlights neuroendocrine transformation as a resistance mechanism to Almonertinib in adenosquamous lung carcinoma.

## Key findings

- The patient's cancer transformed into large cell neuroendocrine carcinoma after 8 months of Almonertinib treatment.
- EGFR mutations persisted even after transformation into neuroendocrine carcinoma.
- Cisplatin and etoposide treatment was effective after transformation.

## Abstract

Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor–sensitizing and T790M resistance mutations. However, resistance to the third-generation EGFR-TKIs is still inevitable. Econdary EGFR mutations, and bypass pathway activation have been reported with Almonertinib therapy. This article presents a rare case report of a patient with EGFR L861Q positive adenosquamous lung carcinoma who transformed into large cell neuroendocrine carcinoma following treatment with Almonertinib. The patient exhibited disease progression 8 months after initiating Almonertinib treatment, and a blood genetic test revealed mutations in EGFR L861Q and EGFR L858R. A subsequent lung biopsy after progression confirmed the diagnosis of large cell neuroendocrine carcinoma, and subsequently treatment with cisplatin and etoposide was effective. Transformation into neuroendocrine carcinoma is one of the mechanisms behind resistance to Almonertinib in adenosquamous lung carcinoma. EGFR mutations may persist even after transformation into neuroendocrine carcinoma. For non-small cell lung cancer patients undergoing Almonertinib therapy, this case report emphasizes the importance of performing a timely pathological biopsy upon the emergence of resistance.

## Linked entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956]
- **Chemicals:** Almonertinib (PubChem CID 121280087), cisplatin (PubChem CID 5460033), etoposide (PubChem CID 36462)
- **Diseases:** adenosquamous lung carcinoma (MONDO:0004973), non-small cell lung cancer (MONDO:0005233)

## Full-text entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}
- **Diseases:** neuroendocrine carcinoma (MESH:D018278), neuroendocrine cancer (MESH:D009369), non-small cell lung cancer (MESH:D002289), large cell neuroendocrine carcinoma (MESH:D018287), adenosquamous lung carcinoma (MESH:D018196)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** L861Q, T790M, L858R

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11876032/full.md

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Source: https://tomesphere.com/paper/PMC11876032