medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-22-2medsovet-7236Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSЛорлатиниб - новые возможности в лечении ALK-позитивных пациентовLorlatinib: new therapeutic options for ALK-positive patientshttps://orcid.org/0000-0002-2154-3376РеутоваЕ. В.ReutovaE. V.

Реутова Елена Валерьевна – кандидат медицинских наук, старший научный сотрудник отделения онкологических лекарственных методов лечения №17 (химиотерапевтическое).

115478, Москва, Каширское шоссе, д. 24

Elena V. Reutova - Cand. Sci. (Med.), Senior Researcher of the Department of Oncological Medicinal Methods of Treatment No. 17 (Chemotherapeutic), Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478

evreutova@rambler.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian Federation2022051220220223640Copyright © Реутова Е.В., 20222022Реутова Е.В.Reutova E.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/7236

Менее чем за 10 лет стандарты лекарственной терапии немелкоклеточного рака легкого (НМРЛ) претерпели колоссальные изменения. Акцент на персонализированный подход в выборе лечебной тактики у больных распространенным НМРЛ дает ощутимые результаты. Выявление пациентов с активирующими мутациями и назначение им таргетной терапии позволило существенным образом улучшить результаты лечения. Транслокации в гене ALK относят к редким мутациям. Как правило, болеют достаточно молодые люди, некурящие или с небольшим стажем курения. Одной из характерных особенностей ALK-позитивного НМРЛ является частое метастазирование в ЦНС, поэтому одним из важных критериев эффективности новых препаратов является оценка их интракраниальной активности. Лорлатиниб - представитель третьего поколения тирозинкиназ (ТКИ) ALK, хорошо проникающий через гематоэнцефалический барьер и обладающий широким спектром противоопухолевой активности в отношении большинства известных мутаций резистентности, которые появляются в процессе таргетной терапии кризотинибом и ТКИ второго поколения. Как и его предшественники, лорлатиниб был первоначально одобрен к применению в качестве второй и третьей линии у пациентов, уже получивших последовательно кризотиниб и один из препаратов второго поколения, либо начавших свое лечение с ТКИ второго поколения. После публикации результатов рандомизированного сравнительного исследования CROWN, продемонстрировавших убедительное преимущество препарата по сравнению с кризотинибом в первой линии лечения, его высокую интракраниальную активность, показания были расширены. В настоящее время лорлатиниб в РФ зарегистрирован для применения у ALK-позитивных больных распространенным немелкоклеточным раком легкого (НМРЛ) как уже получивших таргетную терапию ТКИ ALK первого и/или второго поколения, так и у нелеченных пациентов.

In less than 10 years, the standard of drug therapy for non-small cell lung cancer (NSCLC) has changed tremendously. The emphasis on a personalized approach in the choice of treatment tactics in patients with advanced NSCLC yields tangible results. The identification of patients with activating mutations and the administration of targeted therapy to them has significantly improved the results of treatment. Translocations in the ALK gene are classified as rare mutations. As a rule, these are quite young people, non-smokers or with little experience of smoking. One of the characteristic features of ALK-positive NSCLC is frequent metastasis to the CNS, so one of the important criteria for the effectiveness of new drugs is the assessment of their intracranial activity. Lorlatinib is a third-generation tyrosine kinase (TKI) ALK that penetrates the blood-brain barrier well and has a wide spectrum of antitumor activity against most known resistance mutations that appear during targeted therapy with crizotinib and second-generation TKI. Like its predecessors, lorlatinib was initially approved for second- and third-line use in patients already treated sequentially with crizotinib and one of the second-generation drugs, or starting their treatment with a second-generation TCT. After the publication of the results of the randomized comparative study CROWN, which demonstrated a convincing advantage of the drug compared to crizotinib in the first line of treatment, its high intracranial activity, the indications were expanded. Currently, lorlatinib is registered in the Russian Federation for use in ALK-positive patients with advanced non-small cell lung cancer (NSCLC), both those who have already received targeted therapy for first and/or second generation ALK TKIs, and in untreated patients.

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