Successful management of a ROS1-rearranged pulmonary pleomorphic carcinoma using serial tyrosine kinase inhibitors

Abstract

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.