Targeted therapy of brain metastases in patients with ALK-positive non-small cell lung cancer: A review

The data of recent years indicate the steady increase in the frequency of incidence of brain metastases in many localizations of malignant tumors. Non-small cell lung cancer (NSCLC) is the most common cause, that can affect the central nervous system (CNS). The study of prognostic factors for NSCLC patients with brain metastases, the development of prognostic models, and taking into account the molecular changes can help to approach the development of treatment tactics for this category of patients. The main prognostic factors are age, gender, the Karnofsky’/ECOG status, localization and the number of metastatic foci in the brain, the presence of extracranial metastases, and the histological type of tumor. The discovery of driver mutations and stratification of the cohort of patients with lung adenocarcinoma can open up new potential therapeutic effects in this group of patients, both with primary damage of the CNS and with brain metastases against the background of the therapy. The article deals with the analyzing the literature data and the results of international studies in a group of ALK+ NSCLC patients with brain metastases as well as the mechanisms of lung cancer metastases to the central nervous system and the structure of the blood-brain barrier. The comparative analysis of the treatment of this category of patients using third-generation ALK-inhibitors (alectinib, brigatinib, lorlatinib, crizotinib), the frequency of intracranial response and the possible decision-making algorithm in real clinical practice are presented in detail.