Compound (dual) mutations in EGFR have been previously reported in lung adenocarcinoma and typically include a strong activating mutation combined with a weaker activating mutation. These cases appear to respond well to the EGFR targetted therapies if they include mutations that are known to provide sensitivity to EGFR inhibitor therapies. L858R is a well known activating mutation in exon 21 that is associated with sensitivity to EGFR inhibitors. In vitro functional characterization of mutations at E709 have also been reported to be activivating mutations that are also associated with sensitivity to EGFR inhibitors in vitro. Mutations in E709 often occur together with other muations in EGFR including the L858R mutation.