Guideline: Thoracic Cancer , Living Guidelines

Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations Living Guideline

Guideline Status: Current

Published Online: November 12, 2024

Last Updated: November 12, 2024

Living guidelines are routinely updated guidelines that are developed for selected topic areas with rapidly evolving evidence that drives frequent change in clinical practice. These guidelines are updated on a regular schedule, based on the work of a standing panel that reviews the literature on a continuous basis.  

Lyudmila Bazhenova, Nofisat Ismaila, Fawzi Abu Rous, Krishna Alluri, Janet Freeman-Daily, Balazs Halmos, Narinder Malhotra, Kristen A. Marrone, Sonam Puri, Angel Qin, and Natasha B. Leighl

Updated Recommendations, Version 2024.2

Published online, November 12, 2024, DOI: 10.1200/JCO.24.02133

EGFR Exon 19 Deletion, Evxon 21 L858R Substitution

First-Line Treatment Options Update

Recommendation 1.1. Clinicians should offer osimertinib (Evidence quality: Moderate; Strength of recommendation: Strong).

Recommendation 1.1.1. Clinicians may offer osimertinib with platinum doublet chemotherapy or amivantamab plus lazertinib (Evidence quality: Moderate; Strength of recommendation: Weak).

Second-Line Treatment Options Update

Recommendation 2.2. For patients who have progressive disease on osimertinib or other EGFR tyrosine kinase inhibitors (TKIs) without emergent T790M or other targetable alterations, clinicians may offer platinum-based chemotherapy with or without amivantamab (Evidence quality: Moderate; Strength of recommendation: Strong).

Recommendation 2.2.2. For patients who have progressive disease on EGFR TKI, anti-PD-(L)1 agents with or without platinum chemotherapy are not recommended (Evidence quality: High; Strength of recommendation: Strong).

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The Clinical Practice Guidelines and other guidance published herein are provided by the American Society of Clinical Oncology, Inc. (ASCO) to assist providers in clinical decision making. The information herein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating provider, as the information does not account for individual variation among patients. Recommendations specify the level of confidence that the recommendation reflects the net effect of a given course of action. The use of words like “must,” “must not,” “should,” and “should not” indicates that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating provider in the context of treating the individual patient. Use of the information is voluntary. ASCO does not endorse third party drugs, devices, services, or therapies used to diagnose, treat, monitor, manage, or alleviate health conditions. Any use of a brand or trade name is for identification purposes only.  ASCO provides this information on an “as is” basis and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information, or for any errors or omissions.