EGFR mutations in lung cancers and sensitivity to gefitinib in Chinese

Abstract

7089 Background: Radiographic regressions of tumors treated with gefitinib were observed in 28% of patients in Japan and 10% of those studied in Europe and the U.S. The characteristics of patient response to gefitinib were female, nonsmoker adenocarcinoma and East Asian origin. Recently, two groups have shown that EGFRmutations are associated with sensitivity of NSCLC to gefitinib. There are no any data about EGFR mutation in Chinese. Methods: Frozen tumor specimens from untreated patients with Stage I-IV NSCLC (n = 120) were obtained from Cancer Tissue Bank developed by our hospital. Paraffin-embedded materials were collected retrospectively for patients with NSCLC on gefitinib (n = 15). All 28 exons of EGFR were amplified in 5 specimens and exons 18, 19 and 21 were sought in other specimens. Results: Total 135 cases were enrolled onto the study. The patient characteristic was male: female = 94:31; Adenocarcinoma: other = 82:63; Smoker: nonsmoker =80:55. The mutations of EGFR were detected in 26 patients (25 cases with adeno, 1 with squamous). The EGFR mutation rate was 19.3%(26/135). Heterozygous substitution mutations were detected in exons 21 (11.9% of 16/135) and exons 18 (0.7%, 1/127). In-frame deletions detected in exons 19(8.9%, 12/128). Both substitution mutation and deletion mutation were detected in 3 patients not previously described. For adenocarcinoma subgroup the EGFR mutation rate was 30.5%(25/82). Male adenocarcinoma subgroup the EGFR mutation rate was 30.6%(15/49). Female adenocarcinoma subgroup the EGFR mutation rate was 30.3%(10/33). Smoking male adenocarcinoma the mutation was 53.3%(8/15). Nonsmoking male adenocarcinoma the mutation was 46.7%(7/15). 83.3% of 5/6 patients with positive mutation had clinically significant responses to the Gefitinib. Best response was seen in patients with exons 21 mutation (66.7% of 4/6). Conclusions: The in-frame deletions only occurred in exons 19 and most substitution mutation in exon 21. There was no significant difference of EGFR mutations between male and female, smoker and nonsmoker in Chinese. Lung adenocarcinoma with mutations EGFR are sensitive to Gefitinib. No significant financial relationships to disclose.