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Treatment of Non-Small Cell Lung Cancer with Atypical EGFR Mutations

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Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

EGFR tyrosine kinase inhibitors (TKI) should always be considered when treating advanced/metastatic non-small cell lung cancer (NSCLC) with atypical EGFR mutations. The first choice of TKI depends on the specific mutation(s) present and its effect on structure and function of the EGFR protein. Afatinib is the only EGFR TKI currently FDA approved for atypical EGFR mutations and has the strongest data to support its use in PACC mutations, a subgroup of atypical EGFR mutations which includes G719X and S7681. Dacomitinib may also be an option for these mutations given similar efficacy to afatinib. In contrast, for classical-like mutations such as L861Q, osimertinib should be considered the first choice given that their behavior mimics that of the classical mutations exon 19 deletion and L858R. Osimertinib should also be utilized in the setting of a concurrent T790M mutation. Superior CNS penetrance and well managed toxicity profile may also be reasons to consider osimertinib. Given that the choice of TKI may depend on the specific mutation, it is crucial that every patient diagnosed with NSCLC undergo comprehensive sequencing to identify these mutations.

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  1. Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan, 1500 E. Medical Center Drive, SPC 5848, Med Inn C349, Ann Arbor, MI, 48103, USA

    Leah Wells MD & Angel Qin MD

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Correspondence to Angel Qin MD.

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Leah Wells declares that she has no conflict of interest. Angel Qin has received research funding to institution from Merck, Clovis, Xencor, Genentech, AstraZeneca, and Janssen. She has served as a consultant/advisory board member for Amgen and Strata Oncology.

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Wells, L., Qin, A. Treatment of Non-Small Cell Lung Cancer with Atypical EGFR Mutations. Curr. Treat. Options in Oncol. 24, 1802–1814 (2023). https://doi.org/10.1007/s11864-023-01159-z

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