Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, 2026.3.0

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide evidence-based recommendations for patients with stage IV non–small cell lung cancer with driver alterations. METHODS This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Thirteen studies were identified in the latest search of literature to date. RECOMMENDATIONS Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients with driver alterations. Additional information is available at www.asco.org/thoracic-cancer-guidelines .