Successful Management of a ROS1-Rearranged Pulmonary Pleomorphic Carcinoma Using Serial Tyrosine Kinase Inhibitors

Pulmonary pleomorphic carcinoma (PPC) generally lacks actionable driver mutations such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase or c-ros oncogene 1 (ROS1) rearrangements. The response to crizotinib, ceritinib, brigatinib, and lorlatinib in ROS1-positive advanced non-small cell lung carcinoma is well established; however, there is little mention of their successful administration in pulmonary pleomorphic carcinoma cases. We report a case of a stage II PPC with recurrence after surgical resection and developed multiple distant metastasis. The tumor was refractory to chemotherapy and immunotherapy with progressive disease. EZR-ROS1 fusion was detected by next-generation sequencing and showed a good response to serial ROS1 inhibitors combined with surgery and radiotherapy. Now under lorlatinib, all her lesions responded well during the follow-up with sustained partial remission for more than 18 months. A sustainable treatment effect can be achieved in pulmonary pleomorphic carcinoma with driver mutations with tyrosine kinase inhibitor treatment. Driver mutations should be regularly tested in pulmonary pleomorphic carcinomas.