Prognostic and predictive impact of EGFR and K-ras mutation, and EGFR gene copy number in patients with advanced non-small cell lung cancer (NSCLC) who received first-line cytotoxic chemotherapy

Abstract

8096 Background: Epidermal growth factor receptor (EGFR) mutations, amplification, and K-ras mutations are known as predictive factor of the EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients (pts) with NSCLC. Prognostic influences of those biomarkers remain the matter to be discussed. Methods: Consecutive pts with advanced NSCLC who were examined EGFR genotype and received 1st line cytotoxic chemotherapy were enrolled. EGFR amplification and K-ras mutation were analyzed if sufficient tumor samples were available. Results: 87 pts were enrolled in this study. EGFR mutations or K-ras mutations were found in 26 of 87 (29.9%) or 2 of 65 (3.1%) pts, respectively. As to objective response rate (ORR), no significant differences were observed among pts with EGFR mutations, K-ras mutations, and pts without both mutations. Progression free survival (PFS) in 1st line cytotoxic chemotherapy was 8.4, 1.0, and 3.9 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. PFS was longer in pts with EGFR mutations compared with the pts without both mutations (p=0.0234). We also found the pts with K-ras mutations had shorter PFS compared with pts without both mutations (p=0.0203). Overall survival (OS) was 29.7, 2.3 and 13.4 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. Significant differences were found between pts with EGFR mutation and without both mutations (p=0.0001) and between pts without both mutations and with K-ras mutations (p=0.0001). Pts with EGFR amplification were found in 21 of 78 (26.9%). There were no differences between EGFR amplification positive and negative in terms of ORR, PFS and OS. 87 of 68 (78.2%) pts received EGFR-TKI therapy in the second line or later. As previously reported, both EGFR mutations and amplifications were good predictive marker of ORR, PFS and OS in pts treated with EGFR-TKI. Conclusions: EGFR mutations were good predictive marker and K-ras mutations were poor predictive marker in first line cytotoxic chemotherapy. There is the possibility that EGFR and K-ras mutations have the prognostic impact in advanced NSCLC. [Table: see text]