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ROS1-Rearranged NSCLC After TKI Progression: Current Treatment Options and Emerging Therapeutic Strategies

Slideset

These downloadable slides examine the evolving management of ROS1-rearranged non-small cell lung cancer (NSCLC) after progression on initial ROS1-targeted therapy, with a focus on mechanisms of resistance, central nervous system disease, and selection of subsequent treatment. The content covers guideline-based approaches to limited versus systemic progression and summarizes efficacy and safety data for later-line ROS1 inhibitors, including lorlatinib and repotrectinib, with attention to intracranial activity and outcomes in patients with prior TKI exposure. The activity also explores on-target and off-target resistance mechanisms, including the clinically important ROS1 G2032R solvent-front mutation, bypass signaling pathways, and histologic transformation, and considers how these findings may inform treatment selection at progression. Finally, emerging ROS1-directed strategies and combination approaches are discussed to help learners interpret developing evidence and individualize therapy for patients with treatment-resistant ROS1-positive NSCLC.

Released: August 30, 2026

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Provided by

Provided by Clinical Care Options, LLC dba Decera Clinical Education.

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Supporters

This activity is supported by an educational grant from Nuvation Bio Inc.

Nuvation Bio Inc.

Target Audience

Oncologists, nurse practitioners, physician associates, pharmacists, nurses, and other HCPs caring for patients with non-small-cell lung cancer or thoracic cancer. 

Learning Objectives

Upon completion of this activity, participants should be able to:

  • Implement appropriate molecular testing strategies to accurately identify patients with NSCLC harboring ROS1 rearrangements and other actionable oncogenic drivers

  • Select evidence-based targeted therapies for patients with ROS1-positive NSCLC based on biomarker findings, disease characteristics, current clinical data, and established treatment guidelines

  • Develop and optimize multidisciplinary workflows that support timely comprehensive biomarker testing and accurate detection of ROS1 rearrangements in patients with NSCLC

Financial Disclosures

Primary Author

Benjamin Levy, MD, FASCO: consultant/advisor/speaker: AstraZeneca, DSI, Janssen, Merck, Pfizer, Takeda.

Samuel Rosner, MD: consultant/advisor/speaker: AstraZeneca, Caris Life Sciences, DAVA Oncology, Gilead, MJH Life Sciences, Regeneron.

Additional Disclosures

Generative artificial intelligence (AI) tools were used for data analysis or summarization influencing content. All AI-assisted content underwent human review, editing, and validation by qualified faculty and accredited education staff to ensure scientific accuracy, balance, and compliance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education.