A Case of Lung Adenocarcinoma With Concurrent EGFR Mutation and ALK Fusion - Case Report - Open Access

Sep 29, 2026

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This case underscores the critical importance of retesting for resistant mechanisms, such as EML4-ALK fusion, in patients with EGFR-mutant lung adenocarcinoma who experience rapid progression on EGFR-tyrosine kinase inhibitor (TKI) therapy. Early identification of such co-alterations and an immediate switch to alectinib can lead to rapid and sustained clinical improvement.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Introduction

Case Presentation

Treatment Sequence and Rationale

First-Line Therapy

First Disease Progression and Second-Line Therapy

Clinical Case Reports CASE REPORT OPEN ACCESS A Case ofLung Adenocarcinoma With Concurrent EGFR Mutation and ALK Fusion Combined With Literature Review Yuzhu Chen1,2 | Fei Qi1,2 | Yixin Zeng1,2 | Jingwen Tan1,2 | Mingming Hu1,2 | Hongmei Zhang1,2 | Tongmei Zhang1,2 1Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China | 2Laboratory for Clinical Medicine, Capital Medical University, Beijing, China Correspondence: Tongmei Zhang ([tongmeibj@163.com](tongmeibj@163.com)) Received: 30 July 2025 | Revised: 30 November 2025 | Accepted: 17 December 2025 Keywords: ALK tyrosine kinase inhibitor (ALK-TKI) | anaplastic lymphoma kinase (ALK) fusion | case report | EGFR mutation | EGFR-TKI | lung adenocarcinoma | ABSTRACT
This case underscores the critical importance of retesting for resistant mechanisms, such as EML4-ALK fusion, in patients with EGFR-mutant lung adenocarcinoma who experience rapid progression on EGFR-tyrosine kinase inhibitor (TKI) therapy. Early identification of such co-alterations and an immediate switch to alectinib can lead to rapid and sustained clinical improvement. | | | --- | --- | | 1 | Introduction
In 2022, lung cancer remained the leading cause of global cancer incidence and mortality, with approximately 2.48 million new cases and 1.8 million deaths annually [1] . Non-small cell lung cancer (NSCLC) accounts for the majority of these cases. The discovery of driver mutations, such as in EGFR and ALK, has revolutionized the treatment paradigm for NSCLC [2] . Although EGFR mutations and ALK rearrangements are generally mutually exclusive, their concomitant presence, though rare, presents a significant therapeutic challenge due to the lack of standardized guidelines [3] . This report details a case of concurrent EGFR and ALK alterations and reviews the literature to discuss optimal management strategies.
2 | Case Presentation
A 35-year-old male non-smoker presented in February 2022, with a 20-day history of chest tightness. He had no significant personal or family history of cancer. In January 2022, an external | ultrasound revealed a large pleural effusion; 4400 mL of hemorrhagic fluid was drained via thoracentesis. Pleural fluid analysis showed elevated carcinoembryonic antigen (CEA), suggesting lung adenocarcinoma. A computed tomography (CT) scan confirmed a significant right pleural effusion (Figure 1A: a, b) . Cytology of the effusion confirmed adenocarcinoma cells and was positive for ALK by immunohistochemistry (Figure 2A) . Next-generation sequencing (NGS) of the pleural fluid revealed an EGFR exon 19 deletion (19del) (allele frequency: 5.28%) anda low-abundance EML4-ALK fusion. It is critical to note that this comprehensive molecular profiling was completed prior to initiating any systemic therapy.
A repeat thoracic CT at our hospital in February showed right hilar soft tissue masses, bilateral pulmonary nodules, pleural thickening with effusion, and enlarged right supraclavicularand axillary lymph nodes (Figure 1A: c–e) . A brain MRI in February identified a left frontal lobe nodule, suggestive of metastasis (Figure 1B: a,b). A biopsy of the right lower lung lesion in February confirmed adenocarcinoma and was again positive for ALK fusion (Figure 2B) . The final diagnosis was stage IV | | The first three authors contributed equally to this article. | | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2026 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd. | | Clinical Case Reports, 2026; 14:e71749 1 of 5 [https://doi.org/10.1002/ccr3.71749](https://doi.org/10.1002/ccr3.71749) FIGURE 1 | (A) It describes the changes in chest CT. (B) It describes the changes in brain MRI. (C) It is a timeline

FAQs

Why is retesting important after rapid progression on EGFR-TKI therapy?

Retesting helps uncover resistant mechanisms such as EML4-ALK fusion that may coexist with EGFR mutations. Identifying these co-alterations supports more effective next-line treatment decisions.

What mutations and fusions were detected in this case?

Next-generation sequencing of pleural fluid found an EGFR exon 19 deletion (19del) and a low-abundance EML4-ALK fusion. ALK fusion was also confirmed again through later biopsy testing.

How did the treatment approach change when progression occurred?

First-line therapy used icotinib based on the EGFR sensitizing mutation. After disease progression and identification of relevant co-alterations, the report emphasizes an immediate switch to alectinib for rapid and sustained improvement.

Sep 29, 2026

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