The second-line treatment in advanced NSCLC has been currently proved effective in prolonging overall survival and improving quality of life. Both pemetrexed and erlotinib have been approved for second-line treatment of NSCLC . Erlotinib is a valuable option for the treatment of advanced NSCLC, especially for elderly patients, due to convenience of administration and safety profile. The role of comprehensive geriatric assessment in treatment efficacy and tolerance is an area of investigation.

This trial will compare the efficacy of pemetrexed versus erlotinib in pretreated patients with advanced NSCLC.

Inclusion Criteria:

• Histologically- or cytologically- confirmed Non-Small-Cell Lung Cancer adenocarcinoma
• Stage IIIB/IV
• Failure to prior chemotherapy
• Presence of two-dimensional measurable disease. The measurable disease should not have been irradiated
• Absence or irradiated and stable central nervous system metastatic disease.
• Life expectancy of more than 3 months
• Tissue sample desired for genomic study
• Age ≥ 18 years
• Performance status (WHO) < 3
• For patients > 65 years old: "non-frail" according to comprehensive geriatric assessment
• Adequate bone marrow function (absolute neutrophil count > 1000/mm^3, platelet count > 100000/mm^3, hemoglobin > 9gr/mm^3)
• Adequate liver (bilirubin < 1.5 times upper limit of normal and SGOT/SGPT < 2 times upper limit of normal) and renal function (creatinine < 2mg/dl)
• Presence of a reliable care giver for patients > 65 years old
• Informed consent.

Exclusion Criteria:

• Psychiatric illness or social situation that would preclude study compliance
• Other concurrent uncontrolled illness
• Other invasive malignancy within the past 5 years except nonmelanoma skin cancer