Afatinib plus chemotherapy versus chemotherapy alone after progression on afatinib: new insights on old question?

Epidermal growth factor receptor (EGFR) mutations occur in about 5–10% of non-small cell lung cancer (NSCLC) in non-Asian population and 40–45% Asian population (1,2). Activating EGFRmutations (exon 19 deletion or L858R substitution in exon 21) predict high response rate to first line EGFR tyrosine kinase inhibitors (EGFR-TKIs). Approved EGFR-TKI’s for the treatment of EGFR mutant lung cancer include first generation TKIs (erlotinib and gefitinib) and second generation TKI (afatinib). Third generation EGFR-TKIs have also been developed to target resistance mutation T790M and spare wild type EGFR. Afatinib is an irreversible ERB family blocker that potently inhibits signaling of all homodimers and heterodimers formed by the EGFR, human epidermal growth factor receptor (HER)-2, HER-3, and HER-4 receptors. Afatinib has been evaluated in various settings in LUX-Lung trials summarized in Table 1 (3-9). A subgroup pooled analysis of LUX-Lung 3 and LUX-Lung 6 showed a survival advantage of afatinib over chemotherapy in patients with exon 19 deletion (10).