Coexistence of ALK rearrangement in lung adenocarcinoma harbouring EGFR mutation: Real-World Data From a Single-Institution Experience

Abstract

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.