Background Concomitance of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement have been increasingly reported in lung adenocarcinoma (LUAD). However, the biological mechanism, clinicopathological features and optimization of targeted drugs remain unclear. This study aimed to explore the clinicopathological characteristics of coexisting mutations of EGFR and ALK genes in LUAD patients, with hopes of scientifically guiding such patients towards selected, targeted drugs. Methods Two hundred and thirty-seven cases of LUAD were enrolled. Mutations in exons 18, 19, 20 and 21 of the EGFR gene were detected by the amplification refractory mutation system-peptide nucleic acid (ARMS-PNA) technique, while expression of the ALK fusion gene was detected by the 5′/3′ imbalance strategy for reverse transcription, followed by quantitative polymerase chain reaction (RT–qPCR) analysis. The clinicopathological features of patients with coexisting mutations of EGFR and ALK genes were analysed retrospectively, and the follow-up data of these patients were collected. Results There were 6 cases with coexisting mutations of EGFR and ALK genes, which were more common in women, non-smoking and stage IV LUAD with bone metastasis, hence a positive rate of 2.53% (6/237). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were the first choice for targeted therapy in patients with LUAD harbouring coexisting mutations of EGFR and ALK genes in Gannan region, and the progression-free survival (PFS) was between 2-6 months. Conclusions These results indicated that the positive rate of coexisting mutations of EGFR and ALK genes in LUAD patients in the Gannan region was relatively high; these genes were more common in women, non-smokers and stage IV patients with bone metastasis. EGFR-TKIs were the first choice for targeted therapy in these patients, but the therapeutic effect was limited. EGFR-TKI combined with ALK-TKI dual targeted therapy may be a more effective treatment.

BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement have coexisted in lung adenocarcinoma (LUAD). However, Its biological mechanism, clinicopathological features, and optimization of targeted drugs have not yet been completely elucidated. AIM To explore the clinical profile of LUAD patients with co-mutations of EGFR and ALK genes, with hopes of scientifically guiding similar patients towards selected, targeted drugs. METHODS Two hundred and thirty-seven LUAD patients were enrolled. EGFR mutations were detected by the amplification refractory mutation system-peptide nucleic acid technique, while the expression of ALK rearrangement was screened by the 5′/3′ imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction analysis. The clinicopathological features of these patients were analysed retrospectively, and the follow-up data were collected. RESULTS There were six cases with co-mutations of EGFR and ALK genes, which were more common in women, non-smoking and stage IV LUAD patients with bone metastasis, hence a positive rate of 2.53% (6/237). EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were their preferred drugs for targeted therapy in these patients, with progression-free survival ranging from two months to six months. CONCLUSION In Gannan region, the positive rate of co-mutations of EGFR and ALK genes in LUAD patients is relatively high, and the co-mutations are more common in women, non-smoking and stage IV patients with bone metastasis. These patients prefer EGFR-TKIs as their preferred targeted drugs, but the therapeutic effect is not good. EGFR/ALK dual-TKIs may be more effective targeted drugs, which needs further study.