CASE REPORT article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Long-term survival after ALK-TKI resistance through immunotherapy combined with chemotherapy in ALK-positive non-small cell lung cancer: a case report
Provisionally accepted
- 1Gansu Provincial Cancer Hospital, Lanzhou, China
- 2Lanzhou University First Hospital, Lanzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Anaplastic lymphoma kinase (ALK) gene fusions represent one of the most common driver mutations in non-small cell lung cancer (NSCLC). Currently, targeted drug options for ALK fusion-positive patients exhibit diversity, with third-generation drugs achieving a 5-year progression-free survival (PFS) rate exceeding 60%. Nevertheless, for advanced patients, targeted therapy serves as palliative treatment, with the inevitability of disease progression and the development of therapeutic resistance over time. Yet, there are no unified standards regarding progression patterns, resistance mechanisms, or subsequent treatment strategies. The use of immune checkpoint inhibitors (ICIs) in ALK fusion-positive patients remains highly controversial, and clinical data on whether immune checkpoint inhibitor-based therapy can be administered sequentially after progression on ALK Tyrosine Kinase Inhibitors (ALK-TKI) treatment are limited. This case presents a patient with ALK fusion-positive disease who progressed rapidly after receiving first-generation ALK-TKI followed by second-generation ALK-TKI therapy, along with radiotherapy targeting primary and metastatic lesions. Following chemotherapy combined with immunotherapy, the patient achieved a median response duration of more than 45 months.
Keywords: ALK fusion positivity, Co-mutation, Immunotherapy, target therapy, tislelizumab, TP53
Received: 31 Oct 2025; Accepted: 29 Nov 2025.
Copyright: © 2025 Fu, Yang, Qiao, Liu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiting Liu
Jiexin Wang
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.