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

Abstract

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 EGFR mutations (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).