Goldberg SB, Redman MW, Lilenbaum R, et al. - In patients with treatment-naive EGFR-mutant non–small-cell lung cancer (NSCLC), study authors assessed whether improved progression-free survival (PFS) would result from the combination of afatinib (irreversible ErbB family tyrosine kinase inhibitor) plus cetuximab (EGFR monoclonal antibody) vs afatinib alone by preventing or delaying resistance was investigated in this phase II, multicenter trial. Patients were randomized to receive afatinib 40 mg orally daily plus cetuximab 500 mg/m² intravenously every 2 weeks or afatinib alone. Patients treated with afatinib plus cetuximab did not show improvement in PFS or overall survival, relative to those who received afatinib alone. Despite recognized activity in the acquired resistance setting, no improvement in outcomes was brought about by the combination of cetuximab plus afatinib in previously untreated EGFR-mutant NSCLC. The combination also had greater toxicity with treatment-related grade ≥ 3 adverse events occurring in 72% of patients receiving afatinib plus cetuximab vs with 40% of those receiving afatinib alone