Background: Multiple prospective studies have demonstrated that epidermal growth factor receptor (EGFR) exon 19 and exon 21 mutations are the most powerful predictive biomarkers of response to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). However, there are few studies focused on patients with double mutations compared with a single mutation.
Methods: We retrospectively screened 1,525 samples of Chinese patients with advanced NSCLC who underwent EGFR mutation detections in tumor tissues at Peking University Cancer Hospital between February 2006 and March 2011. Thirty-two cases harboring double mutations were included in this study. The Kaplan-Meier univariate analysis for prognostic factors of survival was applied.
Results: Patients with double mutations accounted for 2.1% (32/1525) of the overall tested samples. Double mutations were more common in female, adenocarcinoma, non-smokers, Eastern Cooperative Oncology Group (ECOG0)-1 and stage IV patients. Twenty-one patients with double mutations were treated with EGFR-TKIs. The objective response rate (ORR) was 23.8%, and the disease control rate (DCR) was 76.2%. In the first-line therapy, the ORR was 16.7%, and the DCR was 66.7%. In univariate analysis, gender, smoking-status, TKI type and TKI response were correlated with progression-free survival, and patients with ECOG 0-1 had longer overall survival.
Conclusions: Patients with double mutations had a low objective response rate when treated with EGFR-TKIs compared with single EGFR exon 19 or exon 21 mutations.
Keywords: DHPLC; double mutations; epidermal growth factor receptor; lung neoplasms; tyrosine kinase inhibitor.