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Future Oncol. 2018 May;14(11):1117-1132. doi: 10.2217/fon-2017-0636. Epub 2018 Jan 16.

Optimizing outcomes in EGFR mutation-positive NSCLC: which tyrosine kinase inhibitor and when?

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Thoracic Oncology, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, 69622, France.
Thoracic Surgery, Institut Curie, Institut du Thorax Curie-Montsouris, Paris, 75248, France.


Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib showed clinical activity in the treatment of T790M-positive disease following progression on a first-line TKI, and is approved in this setting. Recently, osimertinib improved efficacy versus first-generation TKIs (erlotinib and gefitinib) in the first-line setting. Multiple factors can influence first-line treatment decisions, including subsequent therapy options, presence of brain metastases and tolerability, all of which should be considered in the long-term treatment plan. Further research into treatment sequencing is also needed, to optimize outcomes in EGFR mutation-positive non-small-cell lung cancer.


EGFR; T790M; afatinib; dacomitinib; erlotinib; gefitinib; non-small-cell lung cancer; osimertinib; resistance; treatment sequencing

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