P3-156: Different EGFR mutation patterns are associated with survival and response to first-line chemotherapy in NSCLC

EGFR mutations define a subset of NSCLC with sensitivity to gefitinib or erlotinib. However, all EGFR mutations are not equal and may have different predictive and prognostic value. In this study we compared classical “hot spot” and “rare” EGFR mutations in terms of response to 1st line chemotherapy and overall survival in a cohort of patients with advanced NSCLC. Tumor samples were formalin fixed paraffin-embedded tissues that were microdissected to achieve purity 80% in cancer cells. EGFR mutations were analyzed by DNA sequencing of exons 18 to 21 in both forward and reverse directions in PCR products from tumor genomic DNA. Of the 169 patients assessable for mutation detection we found 12 (7%) positive for classical “hot spot” (G719D, Del 19, E746V, L747S, L858R) EGFR mutations and 34 (20%) positive for “rare” EGFR mutations. Classical but not rare mutations were associated with female gender and never smoking history (P=0.002; P<0.001 and P=0.637; P=0.402, respectively). However, the histological type had no significant association with either type of EGFR mutations (P=0.520 and P=0.260, respectively). Response rates to first-line chemotherapy were significantly higher in patients bearing classical mutations (60%) but not in those with rare EGFR mutations (29%) as compared with patients with wild-type EGFR (20.4%) (p=0.005 and p=0.311, respectively). Time to tumor progression was 65 weeks, 22 weeks and 33 weeks for patients with classical mutations, rare EGFR mutations and wild type EGFR, re-spectively (p=0.165 and p=0.327 as compared to wild type). Overall survival was longer in patients bearing classical mutations (p=0.006) but not in those with rare mutations (p=0.843) as compared to patients with wild type EGFR. Different EGFR mutation patterns are associated with higher response to first-line chemotherapy and longer overall survival in patients with advanced NSCLC.