• Afatinib did not improve overall survival (OS) in the overall population in the LUX-Lung 3 and LUX-Lung 6 studies, but OS was improved among patients with EGFR del(19) mutations.
• The data suggest that patients with EGFR exon 21 L858R substitution mutations should be analyzed separately from those with del(19) mutations in the future.

This data set garnered considerable attention when it was first presented because EGFR tyrosine kinase inhibitors (TKIs) have historically resulted in improved progression-free survival (PFS) and response rates in the first-line treatment of EGFR-mutant metastatic disease, but this was the first demonstration of an OS benefit, specifically in the subset of patients with EGFR exon 19 deletion mutations.

Many investigators rethought their positions concerning the choice between erlotinib and afatinib first line as a result of these data, although most, including Dr Spigel, continue to use erlotinib primarily because of the perception that afatinib causes more side effects, particularly gastrointestinal (GI) toxicity and mucositis.

At a global level this study provided more data on the variation in treatment benefit observed depending on type of EGFR mutation, and it seems likely that these considerations will be prospectively integrated into future trial designs.