{"title":"免疫治疗晚期alk重排非小细胞肺癌患者ALK-TKIs进展的疗效","authors":"Danni Wang, Yujing Li, Beibei Liu, Yuqing Lou, Lele Zhang, Yueran Sun, Fangfei Qian, Jun Lu, Fusheng Li, Edyta M Urbanska, Diego Kauffmann-Guerrero, Xinwei Wu, Baohui Han, Yanwei Zhang, Wei Zhang","doi":"10.21037/tlcr-2025-505","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (<i>ALK</i>) rearranged non-small cell lung cancer (NSCLC) remains an unmet need. Among these patients, the efficacy of immunotherapy has not been thoroughly investigated. The purpose of our study was to evaluate the efficacy of immunotherapy in patients with ALK-TKI-resistant NSCLC, stratified by programmed cell death ligand-1 (PD-L1) expression.</p><p><strong>Methods: </strong>We retrospectively collected the data of advanced NSCLC patients with <i>ALK</i>-rearrangement, who were treated with immunotherapy or chemotherapy after the development of ALK-TKI resistance at the Shanghai Chest Hospital. Progression-free survival (PFS) was used to evaluate the outcomes.</p><p><strong>Results: </strong>The final analysis included 89 patients between June 1, 2018, and December 31, 2022, who met the selection criteria. The entire cohort had a median follow-up time of 33.4 months. The patients who received immunotherapy had better PFS than those who received non-immunotherapy (median PFS: 5.3 <i>vs.</i> 2.5 months; P=0.009). The PD-L1-positive patients who received immunotherapy had a median PFS of 7.1 months, while those who received non-immunotherapy had a median PFS of 2.5 months (P=0.02). No such statistically significant difference was observed in the PD-L1-negative patients (median PFS for with immunotherapy <i>vs.</i> without immunotherapy: 1.5 <i>vs.</i> 2.9 months; P=0.68). The PD-L1-positive patients who underwent re-biopsy after the development of TKI resistance and who received immunotherapy had a PFS of 7.8 months, while those who received non-immunotherapy had a PFS of 2.7 months (P=0.002).</p><p><strong>Conclusions: </strong>This was the first real-world retrospective study to show that some patients with positive PD-L1 expression may benefit from immune-based therapy after the development of ALK-TKI resistance. However, we still recommend biopsy for patients who develop ALK-TKI resistance to provide further treatment guidance.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2197-2209"},"PeriodicalIF":3.5000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261234/pdf/","citationCount":"0","resultStr":"{\"title\":\"Efficacy of immunotherapy in advanced <i>ALK</i>-rearranged non-small cell lung cancer patients with disease progression on ALK-TKIs.\",\"authors\":\"Danni Wang, Yujing Li, Beibei Liu, Yuqing Lou, Lele Zhang, Yueran Sun, Fangfei Qian, Jun Lu, Fusheng Li, Edyta M Urbanska, Diego Kauffmann-Guerrero, Xinwei Wu, Baohui Han, Yanwei Zhang, Wei Zhang\",\"doi\":\"10.21037/tlcr-2025-505\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (<i>ALK</i>) rearranged non-small cell lung cancer (NSCLC) remains an unmet need. Among these patients, the efficacy of immunotherapy has not been thoroughly investigated. The purpose of our study was to evaluate the efficacy of immunotherapy in patients with ALK-TKI-resistant NSCLC, stratified by programmed cell death ligand-1 (PD-L1) expression.</p><p><strong>Methods: </strong>We retrospectively collected the data of advanced NSCLC patients with <i>ALK</i>-rearrangement, who were treated with immunotherapy or chemotherapy after the development of ALK-TKI resistance at the Shanghai Chest Hospital. Progression-free survival (PFS) was used to evaluate the outcomes.</p><p><strong>Results: </strong>The final analysis included 89 patients between June 1, 2018, and December 31, 2022, who met the selection criteria. The entire cohort had a median follow-up time of 33.4 months. The patients who received immunotherapy had better PFS than those who received non-immunotherapy (median PFS: 5.3 <i>vs.</i> 2.5 months; P=0.009). The PD-L1-positive patients who received immunotherapy had a median PFS of 7.1 months, while those who received non-immunotherapy had a median PFS of 2.5 months (P=0.02). No such statistically significant difference was observed in the PD-L1-negative patients (median PFS for with immunotherapy <i>vs.</i> without immunotherapy: 1.5 <i>vs.</i> 2.9 months; P=0.68). The PD-L1-positive patients who underwent re-biopsy after the development of TKI resistance and who received immunotherapy had a PFS of 7.8 months, while those who received non-immunotherapy had a PFS of 2.7 months (P=0.002).</p><p><strong>Conclusions: </strong>This was the first real-world retrospective study to show that some patients with positive PD-L1 expression may benefit from immune-based therapy after the development of ALK-TKI resistance. However, we still recommend biopsy for patients who develop ALK-TKI resistance to provide further treatment guidance.</p>\",\"PeriodicalId\":23271,\"journal\":{\"name\":\"Translational lung cancer research\",\"volume\":\"14 6\",\"pages\":\"2197-2209\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-06-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261234/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational lung cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tlcr-2025-505\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational lung cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tlcr-2025-505","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Efficacy of immunotherapy in advanced ALK-rearranged non-small cell lung cancer patients with disease progression on ALK-TKIs.
Background: Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) remains an unmet need. Among these patients, the efficacy of immunotherapy has not been thoroughly investigated. The purpose of our study was to evaluate the efficacy of immunotherapy in patients with ALK-TKI-resistant NSCLC, stratified by programmed cell death ligand-1 (PD-L1) expression.
Methods: We retrospectively collected the data of advanced NSCLC patients with ALK-rearrangement, who were treated with immunotherapy or chemotherapy after the development of ALK-TKI resistance at the Shanghai Chest Hospital. Progression-free survival (PFS) was used to evaluate the outcomes.
Results: The final analysis included 89 patients between June 1, 2018, and December 31, 2022, who met the selection criteria. The entire cohort had a median follow-up time of 33.4 months. The patients who received immunotherapy had better PFS than those who received non-immunotherapy (median PFS: 5.3 vs. 2.5 months; P=0.009). The PD-L1-positive patients who received immunotherapy had a median PFS of 7.1 months, while those who received non-immunotherapy had a median PFS of 2.5 months (P=0.02). No such statistically significant difference was observed in the PD-L1-negative patients (median PFS for with immunotherapy vs. without immunotherapy: 1.5 vs. 2.9 months; P=0.68). The PD-L1-positive patients who underwent re-biopsy after the development of TKI resistance and who received immunotherapy had a PFS of 7.8 months, while those who received non-immunotherapy had a PFS of 2.7 months (P=0.002).
Conclusions: This was the first real-world retrospective study to show that some patients with positive PD-L1 expression may benefit from immune-based therapy after the development of ALK-TKI resistance. However, we still recommend biopsy for patients who develop ALK-TKI resistance to provide further treatment guidance.
期刊介绍：
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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