• Wen Dong, Jinke Zhuge, Pengli Yu, Kai Liu, Mingxing Yang, and Hongkang Wang.
• Department of Respiratory Medicine, Hainan Cancer Hospital, Hainan Province, China.
• Medicine (Baltimore). 2023 Dec 22; 102 (51): e36591e36591.

RationaleCrizotinib has been approved in many countries for the treatment of patients with advanced ROS1-rearranged non-small cell lung cancers (NSCLC). Entrectinib is a ROS1 inhibitor that has been designed to effectively penetrate and remain in the central nervous system (CNS) and has been recommended as first-line therapy. Few reports have precisely described sequential crizotinb followed by entrectinib in patients with ROS1 fusion in later settings.Patient ConcernsA 56-year-old man with a history of occasional smoking visited our hospital with cough, sputum, and shortness of breath.DiagnosisHe was diagnosed with right lung adenocarcinoma (T4N2M1a, stage IV) after image and histological examination, without EGFR or ALK fusion mutation.InterventionsHe received three prior lines of therapies, including chemotherapy, nivolumab monotherapy, and paclitaxel plus anlotinib, with progression-free survival (PFS) of 5, 2, and 11.5 months, respectively. Then the patient began to have headaches and dizziness, and brain magnetic resonance imaging showed multiple brain metastases. Next-generation sequencing (NGS) of the biopsy from neck lymph node identified EZR-ROS1 (1.25% abundance). After 2 months of crizotinib (250 mg daily) plus bevacizumab, all pulmonary and brain lesions decreased, but a small liver lesion was discovered. As treatment went on for another 4 months, the liver lesion continued to grow while other lesions kept decreased or stable state. NGS analysis on the peripheral blood found the disappearance of EZR-ROS1 fusion and a new NTRK2 mutation (c.5C>T, p.Ser2Leu, 0.34% abundance) without other targetable molecular alteration. He received entrectinib (600 mg daily) plus bevacizumab and achieved a partial response. After 7 months of therapy, examination revealed progression of brain lesions.OutcomesThe patient had a total PFS of 13 months from sequential crizotinib and entrectinib therapy.LessonsA ROS1-rearranged NSCLC with CNS metastases responded to sequential tyrosine kinase inhibitors treatment of crizotinb followed by entrectinib. This report has potential implications in guiding decisions for the treatment after crizotinib resistance.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

21 keywords...

hide…