WCLC 2025 - Posters & ePosters-EP.12.01 Real-World Data of ROS-1 Positive Nsclcs- Mutational Heterogeneity, Clinical Characteristics and Its Outcomes

EP.12.01 Real-World Data of ROS-1 Positive Nsclcs- Mutational Heterogeneity, Clinical Characteristics and Its Outcomes

Pdf Summary

This retrospective study analyzed real-world clinical and molecular data of 43 patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) from a cohort of 2,281 patients (1.88%) treated between March 2018 and September 2024 in a community oncology setting. The median patient age was 60 years, with a slight male predominance (M:F ratio 1.15:1), and 10 patients had brain metastases at baseline.<br /><br />Next-generation sequencing (NGS) revealed diverse ROS1 fusion partners, most commonly SDC4, CD74, SLC34A2, and EZR. Co-mutations were present in 34.9% of cases, predominantly involving EGFR (9 patients) and TP53 (5 patients), with one case each of ALK co-mutation. Patients with TP53 co-mutations had notably poorer outcomes, with median overall survival (mOS) of 21.9 months, versus 42.3 months for those with EGFR co-mutations. The overall median follow-up was 32.8 months.<br /><br />Treatment predominantly consisted of tyrosine kinase inhibitors (TKIs) in 89.5% of patients, primarily crizotinib (21 patients), followed by entrectinib (6) and lorlatinib (3). Few patients received chemotherapy alone or combined with TKIs. Some also had upfront brain radiation or surgical resection. Testing methods included NGS, immunohistochemistry, and FISH.<br /><br />The study concludes that although ROS1 rearrangements are rare, first-generation TKIs have significantly improved survival outcomes. However, molecular heterogeneity and presence of co-mutations adversely impact prognosis, underlining the need for comprehensive molecular profiling. Additionally, access to newer-generation TKIs with better central nervous system penetration may further enhance outcomes, especially in patients with brain metastases. This real-world data highlights the clinical complexity and therapeutic challenges in managing ROS1-positive NSCLC.

Asset Subtitle

Kunal Jobanputra

Meta Tag

Speaker Kunal Jobanputra

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

ROS1-positive NSCLC

metastatic non-small cell lung cancer

ROS1 fusion partners

next-generation sequencing

co-mutations EGFR TP53

tyrosine kinase inhibitors

crizotinib entrectinib lorlatinib

brain metastases

molecular heterogeneity

real-world clinical data