Current approaches to therapy of ALK-positive non-small cell lung cancer

Abstract

This article analyzes approaches of the treatment of ALK-positive non-small cell lung cancer (NSCLC). Despite the relatively small percentage of patients with ALK-gene rearrangements, identification of this mutation is very important. The most effective treatment for patients with ALK translocation is the use of ALK inhibitors, which significantly improve survival rates compared to standard chemotherapy. Crisotinib was the first drug approved for the treatment of advanced ALK-positive NSCLC. However, the soon emerging resistance during crizotinib therapy and the inevitable progression of the disease led to the development and introduction into clinical practice of new ALK inhibitors, such as ceritinib and alectinib, the latter of which is currently the best choice for the first-line treatment of metastatic ALK-positive NSCLC. Brigatinib and lorlatinib are drugs that are expected to be registered in the Russian Federation as soon as possible. Lorlatinib, a third generation of ALK and ROS1-kinase inhibitor, allows achieving a high rate of intracranial disease control, and is also effective against acquired resistance mutations during therapy with crizotinib and other ALK inhibitors. The toxicity profiles of each ALK inhibitor are extensively studied and controlled. The wider application of molecular genetic testing and the accumulation of data on resistance mutations will make it possible to correct selection of the next line of treatment. It also became possible to use a combined regimen of immunochemotherapy as the next line of treatment in case of progression against the background of targeted therapy. The available information allows

Keywords

• non-small cell lung cancer
• alk translocation
• alk inhibitors
• resistance
• crizotinib
• lorlatinib
• ceretinib
• alectinib
• brigatinib