Case Report: Tyrosine kinase inhibitors in ROS1-rearranged and granulocyte colony-stimulating factor-producing lung...

c-ros oncogene 1 (ROS1) fusions occur in less than 0.2% of lung squamous cell carcinomas (SqCCs). Concurrent production of granulocyte colony-stimulating factor (G-CSF) induces marked leukocytosis and is associated with aggressive tumor behavior and resistance to conventional therapies. Here, we report a case with this rare and aggressive dual-pathology subtype response to tyrosine kinase inhibitors.

A 53-year-old male smoker with stage IVb SqCC (cT3N3M1) presented marked leukocytosis, and elevated serum G-CSF. The disease progressed following platinum-doublet chemotherapy and immunotherapy, despite a programmed death ligand 1 (PD-L1) tumor proportion score of 50% or greater. Next-generation sequencing revealed an Ezrin (EZR)-ROS1 fusion. Initiation of crizotinib induced rapid partial response and leukocytosis normalization for 6 months. Sequential lorlatinib achieved sustained disease control for 10 months. Due to economic considerations, entrectinib was initiated and that maintained over 15-month ongoing response with minimal toxicity of grade 1 anemia.

This report suggests ROS1 fusion, G-CSF-producing lung SqCC could achieve a favorable response to molecularly-guided therapy with ROS1-tyrosine kinase inhibitors, highlighting a potential therapeutic strategy for this rare subgroup.