Epidermal Growth Factor Receptor (EGFR) targetable mutations have changed the landscape for treatment of advanced stage non-small cell lung cancer in recent years. Three generations of tyrosine kinase inhibitors are now available to target cancers harboring these mutations. The most common EGFR mutations occur in Exons 19 and 21. Exon 18 mutations are extremely rare comprising of 4.1% of all EGFR mutations and the delE709_T710insD mutation accounts for only 0.16% of mutations when occurring as a sole mutation, however, the frequency can vary with the kit utilized for testing. The rarity makes the clinical relevance of these mutations largely unknown. We report a case of a 52year old female with bilateral advanced adenocarcinoma of the lung harboring the delE709_T710insD mutation with significant clinical and radiographic response to treatment with afatinib. We discuss the reported cases of delE709_T710insD mutated non-small cell lung cancer variably treated with geftinib, erlotinib or afatinib. This particular exon 18 mutation seems to preferentially respond to afatinib as reported in two cases including the current case, and in an in vitro experimental model. These reports have implications in guiding decisions for treatment of patients harboring rare EGFR mutations.
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