An expanding role for osimertinib for the treatment of ErbB family driven NSCLC

The discovery that a subset of non-small cell lung cancers (NSCLC) were dependent upon reoccurring activating EGFR (ErbB1) mutations (1-4), primarily deletions of exon 19 or an activating point mutation, L858R, ushered in the era of targeted therapies for lung cancer. Shortly after, first-generation EGFR tyrosine kinase inhibitors (TKIs) that were capable of inhibiting these mutant proteins proved effective. However, the enthusiasm was hampered by the clinical appearance of acquired resistance mediated by a secondary EGFR mutation, converting threonine at position 790 to methionine (T790M) (5), in effect, blocking the ability of the inhibitor to access the ATP binding pocket of EGFR