Roles of EGFR and KRAS Mutations in the Treatment Of Patients With Non-Small-Cell Lung Cancer

After decades of empirical treatment, molecular subtypes of non-small-cell lung cancer (NSCLC) are now emerging that may enable us to target treatment for patients and increase the likelihood of response. Of the biomarkers under evaluation, gene mutations are gaining recognition as predictive markers for anti-epidermal-growth factor receptor (EGFR) therapy. To date, unlike the situation in colorectal cancer, mutation of the v-Ki-Ras-2 Kirsten rat sarcoma viral oncogene homolog (KRAS) has an inconclusive role in NSCLC and should not be used to exclude patients from anti-EGFR therapy. For first-line NSCLC therapy, EGFR mutation status constitutes a prudent test to identify patients who are most likely to benefit from EGFR-tyrosine kinase inhibitor therapy rather than from chemotherapy. In first-line maintenance and relapsed (second-line or third-line) settings, clinical data support the use of erlotinib (Tarceva), as currently indicated, without regard to evaluation of EGFR mutation status. All patient subsets have been shown to benefit with prolonged progression-free and overall survival.