medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-4S-16-22medsovet-6207Research ArticleТАРГЕТНАЯ ТЕРАПИЯ ОПУХОЛЕЙTarget therapy of tumorsСовременные подходы к терапии ALK-позитивного немелкоклеточного рака легкогоCurrent approaches to therapy of ALK-positive non-small cell lung cancerhttps://orcid.org/0000-0003-4469-502XЛактионовК. К.LaktionovК. К.

Лактионов Константин Константинович, д.м.н., профессор, заведующий онкологическим отделением лекарственных методов лечения (химио- терапевтическое) №17

115478, Москва, Каширское шоссе, д. 24 

Konstantin K. Laktionov, Dr. Sci. (Med.), Professor, Head of the Oncological Department of Medicinal Treatment Methods (Chemotherapy) No. 17

24, Kashirskoe Shosse, Moscow, 115478

https://orcid.org/0000-0002-4573-8477КрутелеваС. Ю.KrutelevaS Yu.

Крутелева Светлана Юрьевна, врач-онколог 

115478, Москва, Каширское шоссе, д. 24 

Svetlana Yu. Kruteleva, Oncologist

24, Kashirskoe Shosse, Moscow, 115478

kruteleva2009@mail.ruhttps://orcid.org/0000-0002-2154-3376РеутоваЕ. В.ReutovaЕ. V.

Реутова Елена Валерьевна, к.м.н., старший научный сотрудник

115478, Москва, Каширское шоссе, д. 24 

Elena V. Reutova, Cand. Sci. (Med.), Senior Researcher

24, Kashirskoe Shosse, Moscow, 115478

evreutova@rambler.ruНациональный медицинский онкологический центр имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian Federation20211206202104S1622Copyright © Лактионов К.К., Крутелева С.Ю., Реутова Е.В., 20212021Лактионов К.К., Крутелева С.Ю., Реутова Е.В.Laktionov К.К., Kruteleva S.Y., Reutova Е.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6207

В статье проанализированы современные подходы к лечению ALK-положительного немелкоклеточного рака легкого (НМРЛ). Несмотря на относительно небольшой процент пациентов, имеющих перестройку гена ALK, определение данной мутации является важным этапом обследования пациентов с НМРЛ. Связано это с тем, что наиболее эффективным методом лечения больных с транслокацией ALK является применение ингибиторов ALK, которые значимо улучшают показатели выживаемости по сравнению со стандартной химиотерапией. Кризотиниб был первым таргетным препаратом, одобренным для лечения распространенного ALK- позитивного НМРЛ, и стал препаратом выбора как для пациентов, ранее не получавших лечения, так и для больных, получивших стандартную химиотерапию. Однако возникающая в скором времени резистентность на фоне терапии кризотинибом и неизбежное прогрессирование заболевания привели к разработке и внедрению в клиническую практику новых ингибиторов ALK, таких как церитиниб и алектиниб, последний из которых на данный момент является препаратом выбора для назначения в 1-й линии терапии метастатического ALK-позитивного НМРЛ. Бригатиниб и лорлатиниб – препараты, регистрация которых на  территории РФ ожидается в  скорейшем времени. Лорлатиниб  – ингибитор ALK и ROS1- киназы третьего поколения – позволяет достигнуть высокой частоты интракраниального контроля заболевания, а также эффективен в отношении приобретенных мутаций резистентности на фоне терапии кризотинибом и другими ингибиторами ALK. Профили токсичности каждого ингибитора ALK подробно изучены и управляемы. Более широкое применение молекулярно- генетического тестирования и накопление данных о мутациях резистентности позволит более корректно подобрать следующую линию лечения. Также стало возможным использование комбинированного режима иммунохимиотерапии как следующей линии лечения при прогрессировании на фоне таргетной терапии. Имеющиеся на данный момент сведения позволяют расценивать данную группу пациентов как благоприятную в связи с высокой частотой объективных ответов на проводимую терапию и значимыми улучшениями медиан безрецидивной и общей выживаемости. 

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 

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The authors declare that there are no conflicts of interest present.