• Randomized Phase II study (N = 188) of 2^nd/3^rd-line dacomitinib versus erlotinib in advanced NSCLC
• Median PFS: Overall 2.9 vs 1.9 mo, KRAS wild-type 3.7 vs 1.9 mo, KRAS/EGFR wild-type 2.2 vs 1.8 mo
• Predominantly Grade 1 or 2 skin and GI AEs more frequent with dacomitinib

Most contemporary trials of EGFR TKIs focus on patients with EGFR mutations, but this study in the second- and third-line settings mainly included those with wild-type tumors. In these individuals, along with 30 who had EGFR mutations, a modest PFS advantage was reported in favor of dacomitinib. An ongoing Phase III trial (ARCHER) is comparing dacomitinib to erlotinib after prior chemotherapy again in a genomically unrestricted population, yet at this point we have no convincing evidence that for patients with mutations there is a difference between irreversible TKIs like dacomitinib and afatinib and reversible agents like erlotinib and gefitinib.