Coexistence of anaplastic lymphoma kinase rearrangement in lung adenocarcinoma harbouring epidermal growth factor receptor mutation: A single-center study

ARTICLE HIGHLIGHTS

Research background

Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement are the most two important therapeutic target, which are significantly associated with the sensitivity of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) or ALK-TKIs. At present, EGFR-TKIs and ALK-TKIs are widely used in clinical practice and have exhibited favourable anti-tumour effect in the treatment of non-small cell lung cancer (NSCLC). Accumulating evidences confirm that EGFR mutation and 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.

Research motivation

We retrospectively investigated the clinicopathological features and follow-up data of patients with co-mutations of EGFR and ALK genes in LUAD from a single center, aiming to obtain the clinical profile of LUAD patients with co-mutations of EGFR and ALK genes, with intention to scientifically guide the selection of targeted drugs in similar patients, and ultimately achieve individualized precise treatment.

Research objectives

This study aimed to obtain 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 in similar patients, and ultimately achieve individualized precise treatment.

Research methods

Two hundred and thirty-seven LUAD patients were enrolled. In the experiment, EGFR mutation was detected using amplification refractory mutation system-peptide nucleic acid, and ALK rearrangement was screened by 5′/3′ imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction. The clinicopathological features of these patients were analysed retrospectively, and the follow-up data were collected.

Research results

There were six cases with co-mutations of EGFR and ALK genes, hence a positive rate of 2.53% (6/237), and the co-mutations were more common in women, non-smoking and stage IV LUAD patients with bone metastasis. EGFR-TKIs were their preferred drugs for targeted therapy in these patients, with progression-free survival ranging from two months to six months.

Research conclusions

In Gannan region, the positive rate of co-mutations of EGFR and ALK genes in LUAD patients is relatively high, which may be related to regional heterogeneity, 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.

Research perspectives

In this study, the patients with coexistence of EGFR mutation and ALK rearrangement prefer EGFR-TKIs as their preferred targeted drugs, but the therapeutic effect is not good. Theoretically, EGFR/ALK dual-TKIs may be more effective targeted drugs for NSCLC patients with co-mutations of EGFR and ALK genes, which needs more real cases to confirm. Besides, the cases in this study from a single-Institution enrolled are not large and the collected follow-up data are incomplete, more and more complete cases are needed to further validate our results in multicenter studies in the future. Additionally, the specific subtype of ALK rearrangement in this study is unknown, and its effect on TKIs targeted therapy needs to be further evaluated.