A Case of Acquired Resistance to Immune Checkpoint Inhibitors Caused by <i>EZR-ROS1</i> Fusion Mutation in Lung Adenocarcinoma and Literature Review_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SUN Jiayi ¹ , ZHU Yingying ² , XU Jing ³ , LI Honglin ¹ , LIN Jingwen ¹ ,  LI Yalun ⁴

1. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University; West China Clinical Medical College, Sichuan University, Chengdu, Sichuan 610041, P.R. China;
2. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University / West China Nursing College, Chengdu, Sichuan 610041, P.R. China;
3. Integrated Medical Management Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Institute of Respiratory Health and Multi-Organ Diseases, Chengdu, Sichuan 610041, P.R. China;
4. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China;

Corresponding?author：

LI Yalun, Email: lunlunhx@qq.com

Keywords：

EZR-ROS1 fusion mutation; Acquired resistance; Lung adenocarcinoma; Immune checkpoint inhibitors; Entrectinib

DOI：

10.7507/1671-6205.202601014

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Objective To explore the correlation between EZR-ROS1 fusion mutation and acquired resistance to immune checkpoint inhibitors (ICIs) in patients with lung adenocarcinoma, and to provide a reference for clinical diagnosis and treatment after ICIs resistance.Methods The clinical data of 1 patient with advanced lung adenocarcinoma who developed acquired resistance after receiving ICIs combined with chemotherapy, was found to have EZR-ROS1 fusion mutation by gene detection, and was treated with entrectinib targeted therapy were reported. Combined with the results of literature retrieval, the related mechanisms of ROS1 fusion mutation-induced ICIs resistance were analyzed.Results The 46-year-old female patient was diagnosed with left lower lobe lung adenocarcinoma (cT3N3M1a, stage IVA). She received first-line pemetrexed + carboplatin + sintilimab chemoimmunotherapy combined with maintenance therapy, and achieved sustained partial response (PR) for about 12 months before disease progression. Second-line docetaxel combined with sintilimab therapy was ineffective. Pelvic lymph node biopsy suggested adenocarcinoma metastasis, immunohistochemistry showed ROS1 protein positivity, and next-generation sequencing (NGS) detected EZR-ROS1 fusion mutation (copy number 6.3%). After third-line entrectinib targeted therapy, the efficacy evaluation was sustained PR for 8 months, then the disease progressed again, and the patient eventually died of lung cancer progression and renal failure. No case reports on the correlation between EZR-ROS1 fusion mutation and ICIs acquired resistance in lung adenocarcinoma were found in the literature retrieval. Only 4 cases of lung adenocarcinoma patients with ROS1 fusion mutation (3 cases were CD74-ROS1 fusion) after chemotherapy or ICIs treatment were retrieved, all of which responded to ROS1 tyrosine kinase inhibitor (TKI) treatment but progressed rapidly. Conclusions EZR-ROS1 fusion mutation may be a rare driving mechanism of acquired resistance to ICIs in patients with lung adenocarcinoma. When ROS1 fusion mutation is detected after ICIs resistance, timely switching to ROS1-TKI treatment can achieve short-term efficacy, which provides a new idea for clinical individualized diagnosis and treatment after ICIs resistance.

Citation： SUN Jiayi, ZHU Yingying, XU Jing, LI Honglin, LIN Jingwen, LI Yalun. A Case of Acquired Resistance to Immune Checkpoint Inhibitors Caused by EZR-ROS1 Fusion Mutation in Lung Adenocarcinoma and Literature Review. Chinese Journal of Respiratory and Critical Care Medicine, 2026, 25(6): 408-414. doi: 10.7507/1671-6205.202601014 Copy

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Chinese Journal of Respiratory and Critical Care Medicine

A Case of Acquired Resistance to Immune Checkpoint Inhibitors Caused by EZR-ROS1 Fusion Mutation in Lung Adenocarcinoma and Literature Review

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