EGFR-targeted therapy: at the right time in the right patient
Approximately 11 % of Caucasian patients with NSCLC have tumours that harbour EGFR mutations , which occur in exons 18, 19, 20 and 21 of the EGFR gene. Common mutations include exon 19 in-frame deletions and the exon 21 Leu858Arg point mutation (L858R) . Exon 20 insertions are known to mediate resistance . Little data are available for the other more uncommon mutations. The activating EGFR mutations sensitise lung tumours to EGFR tyrosine kinase inhibitor (TKI) therapies. The irreversible ErbB family blocker afatinib and the reversible EGFR TKIs gefitinib and erlotinib have been approved for first-line therapy of patients with advanced, EGFR-mutation positive NSCLC. The phase IIb LUX-Lung 7 study is the first prospective, global, randomised trial to compare two EGFR-directed therapies (afatinib, gefitinib) in a head-to-head manner in this setting. A total of 319 patients with EGFR-mutated, stage IIIB/IV adenocarcinoma of the lung who had not received any prior treatments for advanced or metastatic disease were randomised to either afatinib 40 mg/day or gefitinib 250 mg/ day. According to the primary analysis, when compared to gefitinib, afatinib significantly improved the co-primary endpoints of PFS (hazard ratio [HR], 0.73; p = 0.017) and time to treatment failure (TTF; HR, 0.73; p = 0.007) . Correspondingly, ORR was significantly superior in the afatinib arm (p = 0.008).