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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.

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