WCLC 2025 - Posters & ePosters-EP.12.42 Durable Response to ROS1-Tkis in Metastatic Squamous NSCLC With EZR-ROS1 Fusion

Pdf Summary

This case study reports on an 82-year-old male patient with metastatic pulmonary squamous cell carcinoma (SqCC), who demonstrated a durable response to ROS1 tyrosine kinase inhibitors (ROS1-TKIs) due to an identified EZR-ROS1 gene fusion. While molecular testing is not standard in metastatic SqCC, it was performed here to explore additional treatment options. Initial diagnosis was confirmed by biopsy and immunohistochemistry showing SqCC markers (p40 positive, TTF1 negative) with a PD-L1 tumor proportion score of 50%.<br /><br />Comprehensive molecular analysis using RNA-next generation sequencing (NGS) identified a novel EZR exon 9-ROS1 exon 34 fusion, and DNA-NGS detected a pathogenic TERT promoter mutation (C228T). Guided by these findings, sequential treatment with ROS1-TKIs was initiated, resulting in an exceptional objective clinical response with ongoing progression-free survival of 49 months at the time of report.<br /><br />This case is notable as it is reportedly the first documented instance of metastatic pulmonary SqCC harboring an EZR-ROS1 fusion responding to ROS1-targeted therapy, highlighting the clinical utility of incorporating both RNA- and DNA-based molecular testing in selected SqCC patients. The durable therapeutic benefit seen here reinforces the importance of molecular profiling beyond standard histological assessment, particularly in patients without typical driver mutations. This approach may enable identification of rare but actionable genetic alterations, providing effective targeted treatment strategies in metastatic pulmonary SqCC cases traditionally treated with limited precision options.

Asset Subtitle

Edyta Urbanska

Meta Tag

Speaker Edyta Urbanska

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

metastatic pulmonary squamous cell carcinoma

EZR-ROS1 gene fusion

ROS1 tyrosine kinase inhibitors

RNA-next generation sequencing

DNA-next generation sequencing

TERT promoter mutation

molecular profiling

PD-L1 tumor proportion score

targeted therapy

progression-free survival