Julia Rotow, MD

Julia Rotow, MD, of Dana-Farber Cancer Institute, reviews primary results of the phase 3 DESTINY-Lung04 trial showing first-line trastuzumab deruxtecan improved progression-free survival and response rate compared with pembrolizumab plus platinum chemotherapy and pemetrexed in patients with metastatic HER2-mutant non-small cell lung cancer.

Julia K. Rotow, MD, discusses why dual EGFR inhibition prevented acquired resistance mutations but did not extend PFS, and where the combination fits now.

Julia K. Rotow, MD, discusses how T-DXd, zongertinib, and sevabertinib may be sequenced in first-line HER2-mutant NSCLC and why resistance profiling at progression matters.

Julia K. Rotow, MD, discusses subgroup results and post-progression treatment imbalances in the phase 3 DESTINY-Lung04 trial of first-line T-DXd in HER2-mutant NSCLC.

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

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

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

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

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 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. 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.

Drs Rotow and Dietrich discuss the significance of the accelerated FDA approval of zongertinib (Hernexeos) for patients with HER2 TKD–mutated NSCLC.

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.

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 treatment selection, resistance challenges, and future directions in managing BRAF-mutated lung cancer.

Panelists discuss the latest trial results supporting dual-pathway inhibition in BRAF-mutated metastatic lung cancer.

Drs Rotow and Woodard talk through recent updates to the perioperative non–small cell lung cancer treatment paradigm.

Panelists discuss combination targeted approaches for managing BRAF-mutated lung cancer and their impact on disease durability.

Panelists discuss evolving treatment approaches for BRAF-mutated metastatic lung cancer and their clinical impact.

Explore a case study on HER2 mutant lung cancer treatment, highlighting challenges, responses, and the importance of monitoring for ILD.

Panelists discuss the biology and clinical implications of BRAF mutations in non–small cell lung cancer (NSCLC).

Panelists discuss individualized treatment selection based on age, comorbidities, and patient preferences in ALK-positive lung cancer.

Explore a case study on HER2 mutant lung cancer treatment, highlighting challenges, responses, and the importance of monitoring for ILD.

Explore a case study on HER2 mutant lung cancer treatment, highlighting challenges, responses, and the importance of monitoring for ILD.

Panelists discuss novel research directions aimed at overcoming resistance and extending survival in ALK-positive lung cancer.

Panelists discuss mechanisms of acquired resistance to ALK inhibition and how molecular testing guides sequencing strategies.

Explore a case study on HER2 mutant lung cancer treatment, highlighting challenges and responses to chemotherapy and immunotherapy.

Explore a case study on HER2 mutant lung cancer treatment, highlighting challenges, responses, and the importance of monitoring for ILD.