Evaluation of epidermal growth factor receptor (EGFR) mutations as predictive and prognostic indicators in patients with adenocarcinoma of the lung treated with conventional chemotherapy

Abstract

7165 Background: EGFR mutations are associated with the responses to EGFR-tyrosine kinase inhibitors (TKI) in patients (pts) with adenocarcinoma of the lung. The E746-A750 deletion and L858R substitution mutations are the most common, as previously described. However, their implications in pts treated with conventional chemotherapy are unclear. To evaluate the predictive and prognostic value of the EGFR mutations, we studied pts with adenocarcinoma of the lung treated with conventional chemotherapy. Methods: We reviewed pts with advanced or recurrent chemotherapy naïve adenocarcinoma of the lung who received systemic chemotherapy between January 1999 and July 2001. Deletion in exon 19 and missense mutation (L858R) in exon 21 from small biopsy or cytology samples were analyzed by a high-resolution DNA melting analysis technique. Results: A total of 101 pts, all Japanese, could be analyzed. Patient characteristics were as follows: median age: 62 (37–84) years; female/ male: 39/ 62; never/ former/ current smoker: 47/ 23/ 31; and platinum-based/ non-platinum regimen: 81/ 20 (18 pts received EGFR-TKI later). 43 pts (42.6%) had EGFR somatic mutations; deletion in 24 pts, and a point mutation (L858R) in 19 pts. PR/ SD/ PD/ NE was observed in 11/ 24/ 7/ 1 pts with EGFR mutations and in 13/ 28/ 15/ 2 pts without the mutations, respectively. The response rate was similar (26% vs. 22%, p = .71) in the two subgroups. The median survival duration of the pts with EGFR mutations was 14.9 months (n = 43, including the 11 pts treated with EGFR-TKI later), as compared with 11.0 months (n = 58, including the 7 pts treated with EGFR-TKI later) in the pts without EGFR mutations (p = .09). Another analysis which handle the start of gefitinib administration as a censoring showed similar results (p = .24). Conclusions: EGFR mutations were not good predictors of tumor response to conventional chemotherapy. The overall survival tended to be longer in the pts with EGFR mutations, but prognostic value of these mutations for survival in pts with advanced adenocarcinoma of the lung was not statistically significant. No significant financial relationships to disclose.