Unprecedented 60-month progression-free survival with reduced-dose crizotinib in a patient with ROS1-rearranged lung squamous cell carcinoma: a case report and literature review

We report a case of a 70-year-old female diagnosed with ROS1-positive advanced squamous non-small cell lung cancer (NSCLC). Her PD-L1 expression was 3% (assay 22C3). The patient experienced disease progression after initial treatment with carboplatin, nab-paclitaxel, and pembrolizumab, and was subsequently switched to crizotinib 250 mg twice daily. Early during treatment, the patient developed severe esophagitis. Following a dose reduction to 250 mg once daily, the symptoms resolved and did not recur. On follow-up, significant absorption of the primary lung lesion and metastatic sites was observed, assessed as a near-complete response according to RECIST version 1.1 criteria. The patient's quality of life markedly improved. To date, she has continued crizotinib therapy for nearly 60 months without disease progression, representing the longest progression-free survival (PFS) reported to date for a patient with ROS1-positive lung squamous cell carcinoma. This case not only demonstrates the durable efficacy of crizotinib in ROS1-rearranged squamous carcinoma but also indicates that long-term disease control may be achievable with crizotinib even at a reduced dose. Furthermore, our observation of severe esophagitis as a rare adverse event underscores the importance of dose adjustment in adverse event management, which can lead to long-term survival benefits for patients. This case highlights the critical importance of routine molecular testing in squamous cell carcinomas to avoid missing potential candidates who may benefit from targeted therapy.