Efficacy and long-term survival of advanced lung adenocarcinoma patients with uncommon EGFR mutations treated with 1st generation EGFR-TKIs compared with chemotherapy as first-line therapy.

PURPOSE: This study aims to understand the effects and long-term survival of 1st generation epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)or platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations.

PATIENTS AND METHODS: Specimens from 4276 advanced (IIIB/IV) patients were diagnosed with lung adenocarcinoma and underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University. The clinic characteristics, survival outcomes data, treatment outcomes and data of subsequent therapies after first-line treatment were collected of patients with uncommon EGFR mutations. The results were compared with common EGFR mutations.

RESULTS: For patients with uncommon EGFR mutations, EGFR-TKIs or platinum-based chemotherapy as first-line therapy, showed no difference in objective response rate (ORR 33% vs 27.1% P = 0.499) and disease control rate (DCR 76.5% vs 87.5%, P = 0.194). EGFR-TKIs showed a superior progression-free survival than chemotherapy (median PFS, 7.2 vs 4.9 mt, HR = 0.604; P = 0.0088). Interestingly, compared with chemotherapy, we found that overall survival (median OS, 14.3 vs 20.7 mts, HR = 1.759; P = 0.0336) was significantly worse in patients with EGFR-TKIs. Multivariate analysis showed that extra metastases (HR = 2.240, P = 0.001) and smoking history (HR = 2.048, P = 0.013) were independent prognostic factors for OS in lung adenocarcinoma patients with EGFR uncommon mutations.

CONCLUSIONS: Compared with chemotherapy, use of the 1st generation of EGFR-TKIs as first-line therapy can improve the short-term efficacy of patients with EGFR uncommon mutations advanced lung adenocarcinoma, but platinum-based chemotherapy showed a longer overall survival.