Optimizing Care for ROS1-Positive Non-Small Cell Lung Cancer

Panelists discuss strategies for identifying and managing ROS1-positive NSCLC, focusing on comprehensive testing approaches, emerging clinical data, and factors that guide treatment decisions.

Panelists discuss the role of ctDNA (liquid biopsy) in clinical practice, highlighting its benefits and limitations in detecting actionable mutations, interpreting results, and guiding treatment decisions when tissue testing is insufficient.

Dr. Leal emphasizes that although actionable genomic alterations like ROS1 are rare, their clinical implications are enormous. Following National Comprehensive Cancer Network (NCCN) guidelines, these targets should be acted upon in the first-line setting as the initial targeted therapy treatment.

Dr. Wistuba provides detailed information about ROS1 gene fusions, discovered in the 1980s with over 30 to 40 fusion partners identified that constitutively activate ROS1 in cells, leading to malignant properties.

Dr. Wistuba confirms that fusion variant identification does not impact treatment selection, emphasizing that ROS1-positive versus ROS1-negative status represents the key clinical decision point.

Dr. Wistuba addresses the complexity of NGS reports that may include multiple abnormalities beyond ROS1 fusions.

Dr. Wistuba explains that acquired resistance to ROS1-targeted therapies frequently involves on-target mutations, with G2032R representing the most frequently observed resistance mutation among 10 to 12 described mutations that affect the ATP binding site and reduce drug binding efficiency.

Dr. Rodriguez reviews historical toxicity profiles from earlier ROS1 inhibitors, noting that crizotinib and entrectinib presented novel side effects including visual field changes preventing night driving due to floaters, along with liver function test (LFT) abnormalities requiring monitoring.

Dr. Rodriguez outlines patient education strategies emphasizing partnership from treatment initiation, as clinical trials demonstrate over half of patients require dose adjustments.

Dr. Leal outlines her approach to frontline treatment selection for newly diagnosed patients with ROS1-positive lung cancer.

Dr. Wistuba emphasizes the critical need for reinforcing RNA testing alongside DNA testing for comprehensive NGS in lung cancer.