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CASE REPORT article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1522542
Crizotinib for ROS1 SCLC Case report: Durable response of immuno-chemotherapy targeting a rare ROS1 fusion-positive extensive-stage SCLC patient after primary resistance to crizotinib
Provisionally accepted
Mengli Qiu1,2
Sisi Wang1
Peiwen Guo1,2
Yong Zhu1,2Siqi Wu1,2Huiting Peng1,2
Zehuai Guo3Yanmeng Guo4Jieheng Lin1*Yang Cao1*- 1The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
- 2First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
- 3Cancer Hospital, College of Medicine, Shantou University, Shantou, Guangdong Province, China
- 4The First Clinical Medical School, Hubei University of Chinese Medicine, Hubei, China
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Background: Small cell lung cancer (SCLC) is characterized by an exceedingly low mutation rate in oncogenic driver alterations, and there are currently no articles or case reports documenting SCLC patients carrying ROS1 fusions. Tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy and safety in patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC).However, effective treatment modalities for ROS1 fusion-positive SCLC patients remain poorly defined.We report the first case of an extensive-stage SCLC (ES-SCLC) patient harboring ROS1 fusion, along with TP53, RB1, PTEN, and TERT mutations. The patient exhibited primary resistance to a three-week course of crizotinib as first-line treatment. Following this, the patient was administered second-line therapy, including chemotherapy coupled with immune checkpoint inhibitor (ICI) and ICI maintenance treatment, resulting in a partial response (PR).Notably, the clinical response to second-line therapy persisted for over 19 months, surpassing the previously reported efficacy of immuno-chemotherapy in ES-SCLC cases (5.7 months) while maintaining a satisfactory quality of life.We hypothesize that ROS1 fusion may not function as an oncogenic driver alteration in ES-SCLC. Immuno-chemotherapy, not ROS1-TKIs, might provide superior efficacy in ES-SCLC patients with ROS1 fusion.
Keywords: SCLC, ROS1, crizotinib, Immunotherapy, chemotherapy, primary resistance
Received: 04 Nov 2024; Accepted: 18 Apr 2025.
Copyright: © 2025 Qiu, Wang, Guo, Zhu, Wu, Peng, Guo, Guo, Lin and Cao. 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:
Jieheng Lin, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Yang Cao, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
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.