medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-251medsovet-8367Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSЭволюция терапии ALK-позитивных карцином легкого: применение ALK-ингибиторов третьего поколения в реальной клинической практикеEvolution of therapy for ALK-positive lung carcinomas: Application of third-generation ALK inhibitors in real clinical practicehttps://orcid.org/0000-0001-8340-7962НасретдиновА. Ф.NasretdinovA. F.

Насретдинов Айнур Фанутович - врач-онколог, заведующий отделением противоопухолевой лекарственной терапии №2.

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Ainur F. Nasretdinov - Head of the Department of Antitumor Drug Therapy No. 2.

73/1, Oktyabrya Ave., Ufa, 450054

ainur_doc@mail.ruhttps://orcid.org/0000-0003-0996-5995СултанбаевА. В.SultanbaevA. V.

Султанбаев Александр Валерьевич - к.м.н., заведующий отделом противоопухолевой лекарственной терапии.

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Aleхandеr V. Sultanbaev - Cand. Sci. (Med.), Head of the Department of Anticancer Drug Therapy.

73/1, Oktyabrya Ave., Ufa, 450054

rkodrb@yandex.ruhttps://orcid.org/0000-0003-1185-977XМусинШ. И.MusinSh. I.

Мусин Шамиль Исмагилович - к.м.н., заведующий хирургическим отделением №6.

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Shamil I. Musin - Cand. Sci. (Med.), Head of the Surgery Department No. 6.

73/1, Oktyabrya Ave., Ufa, 450054

musin_shamil@mail.ruhttps://orcid.org/0000-0003-3734-2779МеньшиковК. В.MenshikovK. V.

Меньшиков Константин Викторович - к.м.н., врач-онколог отдела химиотерапии, Республиканский клинический онкологический диспансер; доцент кафедры онкологии с курсами онкологии и патологической анатомии Института дополнительного профессионального образования, Башкирский ГМУ.

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Konstantin V. Menshikov - Cand. Sci. (Med.), Oncologist of the Department of Anticancer Drug Therapy, RCOD; Associate Professor of the Department of Oncology with courses in Oncology and Pathological Anatomy at the IAPE

73/1, Oktyabrya Ave., Ufa, 450054; 3, Lenin St., Ufa, 450000

kmenshikov80@bk.ruhttps://orcid.org/0000-0002-6769-7194АюповР. Т.AyupovR. T.

Аюпов Рустем Талгатович - к.м.н., заместитель главного врача по медицинской части.

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Rustаm T. Ayupov - Cand. Sci. (Med.), Deputy Chief Physician for the Medical Department.

73/1, Oktyabrya Ave., Ufa, 450054

ru2003@bk.ruhttps://orcid.org/0000-0002-8461-9243ИзмайловА. А.IzmailovA. A.

Измайлов Адель Альбертович - д.м.н., главный врач.

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Adel A. Izmailov - Dr. Sci. (Med.), Chief Physician.

73/1, Oktyabrya Ave., Ufa, 450054

izmailov75@mail.ruhttps://orcid.org/0000-0002-7082-0085СеребренниковГ. А.SerebrennikovG. A.

Серебренников Григорий Андреевич - врач-онколог отделения противоопухолевой лекарственной терапии №2.

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Grigory A. Serebrennikov - Oncologist, Department of Antitumor Drug Therapy No. 2.

73/1, Oktyabrya Ave., Ufa, 450054

g.serebrennikov@mail.ruhttps://orcid.org/0000-0003-0988-7261АскаровВ. Е.AskarovV. E.

Аскаров Вадим Евгеньевич - заведующий отделением филиала.

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Vadim E. Askarov - Head of the Branch Office.

73/1, Oktyabrya Ave., Ufa, 450054

ufa.askarov@gmail.comhttps://orcid.org/0009-0009-9270-8172ФеоктистовД. В.FeoktistovD. V.

Феоктистов Дмитрий Владимирович - врач-онколог, заведующий отделением абдоминальной онкологии №2.

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Dmitriy V. Feoktistov - Head of the Department of Abdominal Oncology No. 2.

73/1, Oktyabrya Ave., Ufa, 450054

dimafeoktistov@mail.ruРеспубликанский клинический онкологический диспансерРоссияRepublican Clinical Oncology DispensaryRussian FederationРеспубликанский клинический онкологический диспансер; Башкирский государственный медицинский университетРоссияRepublican Clinical Oncology Dispensary; Bashkir State Medical UniversityRussian Federation2024240720240107480Copyright © Насретдинов А.Ф., Султанбаев А.В., Мусин Ш.И., Меньшиков К.В., Аюпов Р.Т., Измайлов А.А., Серебренников Г.А., Аскаров В.Е., Феоктистов Д.В., 20242024Насретдинов А.Ф., Султанбаев А.В., Мусин Ш.И., Меньшиков К.В., Аюпов Р.Т., Измайлов А.А., Серебренников Г.А., Аскаров В.Е., Феоктистов Д.В.Nasretdinov A.F., Sultanbaev A.V., Musin S.I., Menshikov K.V., Ayupov R.T., Izmailov A.A., Serebrennikov G.A., Askarov V.E., Feoktistov D.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/8367

Рак легкого в настоящее время является разнородной группой заболеваний, его гетерогенность обусловлена не только фенотипическим, но и генетическим профилем. Особое место занимают подтипы, имеющие драйверные мутации. Благодаря новым противоопухолевым агентам – ингибиторам малых молекул стало возможным значительно увеличить шансы пациентов на выживание. В диагностическую панель чаще всего входят мутации в генах EGFR, ALK, ROS1, BRAF, несколько реже определяются генетические изменения в МET, KRAS, HER2, NTRK и др. Такое распределение, скорее всего, объясняется доступностью соответствующих ингибиторов. В статье приводится обзор ALK-ингибиторов разных поколений, применяемых в Российской Федерации, среди которых – кризотиниб, церитиниб, алектиниб и лорлатиниб. Указанные препараты входят в клинические рекомендации по лечению ALK-позитивных карцином легкого всех крупных онкологических сообществ. В статье также описаны результаты регистрационных исследований, доказывающих преимущество ALK-ингибиторов перед стандартной терапией, в том числе исследования СROWN. В указанном исследовании представитель последнего поколения ALK-ингибиторов лорлатиниб демонстрирует превосходство над кризотинибом со снижением риска прогрессирования или смерти на 73% и лучшие показатели интракраниального ответа. Приводится описание клинического случая лечения метастатического рака легкого с применением ALK-ингибитора третьего поколения лорлатиниба. Препарат был назначен в первой линии терапии. Результат лечения пациента указывает на высокую эффективность лорлатиниба в первой линии лечения рака легкого с транслокацией ALK наряду с низкой токсичностью. Период лечения составляет уже более 70 мес., пациент продолжает терапию на момент последнего контроля. Зарегистрирован полный ответ на терапию лорлатинибом. На фоне лечения были зарегистрированы нежелательные явления: гипертриглицеридемия 1-й степени токсичности, гиперхолестеринемия 2-й степени токсичности, повышение печеночных трансаминаз 1-й степени токсичности.

Lung cancer is currently a heterogeneous group of diseases, whose heterogeneity is determined not only by its phenotypic, but also by its genetic profile. A special place is occupied by subtypes that have driver mutations. Due to new antitumor agents – small molecule inhibitors – it has become possible to significantly increase patients’ chances of survival. The diagnostic panel most often includes mutations in the EGFR, ALK, ROS1, BRAF genes; somewhat less frequently, genetic changes in MET, KRAS, HER2, NTRK, etc. are determined. This distribution is most likely explained by the availability of appropriate inhibitors. The article provides an overview of different generations of ALK inhibitors known in the Russian Federation, among them the most famous: crizotinib, ceritinib, alectinib and lorlatinib. These drugs are included in the clinical guidelines for the treatment of ALK-positive lung carcinomas of all major oncology societies. The article describes the results of registration studies proving the advantage of ALK inhibitors over standard therapy, including the results of the CROWN study. In this study, the latest generation of ALK inhibitors, lorlatinib, demonstrates superiority over crizotinib, with a 73% reduction in the risk of progression or death and better intracranial response rates. A description of a clinical case of treatment of metastatic lung cancer using the third generation ALK inhibitor lorlatinib is provided. The drug was prescribed in the first line of therapy. The patient’s treatment outcome indicates high efficacy of lorlatinib in the first-line treatment of ALK translocation-positive lung cancer, along with low toxicity. The treatment period has already been more than 70 months and the patient continues therapy at the time of the last control. A complete response to lorlatinib therapy was recorded. During treatment, the following adverse events were recorded: hypertriglyceridemia, grade 1 toxicity, hypercholesterolemia, grade 2 toxicity, increased liver transaminases, grade 1 toxicity.

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