Clinical efficacy of targeted therapy towards metastatic lung cancer carrying distinct types of ALK rearrangements

Introduction. Translocations of ALK receptor tyrosine kinase occur in approximately 5-9 % of lung adenocarcinomas. The use of ALK inhibitors usually results in the reduction of tumor size. Nevertheless, the extent and duration of response can vary significantly. The aim of the study is to summarize the available information on the predictive role of various types of ALK translocations in response to ALK inhibitors. Material and methods. The review presents the data from relevant laboratory and clinical studies published in PubMed database, as well as the authors' own results. Results. A number of experiments on cell cultures have demonstrated that the structure of ALK fusion affects the properties of the resulting chimeric protein, in particular its stability and sensitivity to crisotinib action. The few available clinical trials, evaluating the effect of ALK inhibitors depending on the type of translocation, showed heterogeneous results. While some of them detected associations between the so-called «short» variants of EML4-ALK rearrangements and worse survival when using crisotinib in comparison with the EML4-ALK type 1 variant, the others failed to confirm these observations. The study of 64 Russian patients receiving ALK inhibitors also did not support the effect of different ALK translocation variants on progression-free survival or objective response rate. Conclusions. There is a diversity of reported associations, with none of them characterized by sufficient reproducibility. Current evidences do not support the predictive role of ALK variants.