<qa>  What is the primary endpoint of freedom from progression?To address these issues we propose a phase I randomized study of concurrent pemetrexedcetuximab compared to sequential cetuximabpemetrexed therapy for the second-line treatment of advanced NSCLC. Patients will be randomized at study entry. Regarding prospective analysis of the rapid-rash forming phenotype, all patients will receive 2 weeks of initial treatment with cetuximab and undergo formal rash evaluation, serum and skin collection. According to the initial randomization, half of the study subjects will continue with cetuximab monotherapy while the remainder will receive concurrent cetuximab and pemetrexed. The primary study endpoint of freedom from progression and secondary endpoint of objective response rate will be based on the comparison of patients in he concurrent therapy group with patients treated with cetuximab monotherapy with Day-14 first receipt of cetuximab as the reference treatment start date. Overall survival will be analyzed as a secondary endpoint to assess the efficacy of concomitant treatment with cetuximab and pemetrexed compared to sequential treatment with cetuximab followed by pemetrexed upon disease progression. As patients in both treatment arms receive cetuximab, correlative studies will be performed on all enrolled patients. For serum proteomic studies designed to identify a serum polypeptide signature associated with response to cetuximab-based therapy, serum samples shall be collected at enrollment, and just prior to receiving the third dose of cetuximab therapy. To provide the opportunity to perform retrospective pharmacogenomic studies, whole blood DNA will be collected from each patient at enrollment and subsequently analyzed for candidate gene polymorphisms once outcome data is available. Finally, an alternative approach to identification of markers for responsiveness to EGFR inhibition already in progress at the University of Chicago entails collection of skin biopsies before and after treatment with an EGFR inhibitor. 