• The combination of afatinib and cetuximab demonstrated efficacy in patients (n = 126) with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib regardless of EGFR T790M mutation status.
• The safety profile of this combination was manageable.

This is the first publication of data from a Phase Ib trial of the afatinib/cetuximab combination in patients with disease progression on an EGFR TKI. Preclinical work by Dr William Pao and others suggested synergy between these agents, and the results of this study were indeed encouraging, with almost all patients experiencing some degree of disease control. The obvious problem with this regimen is toxicity, particularly dermatologic issues.

For patients with T790M tumor mutations, clearly third-generation TKIs result in less toxicity and perhaps greater efficacy compared to this combination, but some investigators consider afatinib/cetuximab for patients without T790M mutations, although chemotherapy is a more common choice. With the explosion of interest in new TKIs, future research on this combination is perhaps in limbo, but a major randomized Intergroup trial of afatinib alone or with cetuximab for the first-line treatment of metastatic EGFR-mutant disease is ongoing.