medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-20-15-21medsovet-5929Research ArticleИММУНОТЕРАПИЯ В ОНКОЛОГИИImmunotherapy in oncologyПерспективы применения ингибиторов контрольных точек PD-1/PD-L1 при злокачественных новообразованиях желудка и пищеводно-желудочного переходаProspects of application of inhibitors of PD-1/PD-L1 checkpoints in malignant tumors of the stomach and esophagogastric junctionhttps://orcid.org/0000-0003-4341-6017СакаеваД. Д.SakaevaD. D.

Сакаева Дина Дамировна, доктор медицинских наук, профессор, заместитель главного врача по онкологии  

450071, Республика Башкортостан, Уфа, Лесной проезд, д. 4

Dina D. Sakaeva, Dr. of Sci. (Med.), Professor, Deputy Chief Medical Officer for Oncology

4, Lesnoy proezd, Ufa, Republic of Bashkortostan, 450071

d_sakaeva@mail.ruhttps://orcid.org/0000-0001-9137-5534МельниковаА. А.MelnikovaA. A.

Мельникова Ангелина Александровна, врач-онколог, амбулаторное отделение противоопухолевой лекарственной терапии

450054, Республика Башкортостан, Уфа, проспект Октября, д. 73/1

Angelina A. Melnikova, Oncologist, Ambulatory Department of Anticancer Drug Therapy

73/1, Oktyabrya Avenue, Ufa, Republic of Bashkortostan, 450054

sitnikangela@gmail.comКлинический госпиталь «Мать и Дитя»РоссияClinical Hospital “Mother and Child”Russian FederationРеспубликанский клинический онкологический диспансерРоссияRepublican Clinical Oncology DispensaryRussian Federation2020171220200201521Copyright © Сакаева Д.Д., Мельникова А.А., 20202020Сакаева Д.Д., Мельникова А.А.Sakaeva D.D., Melnikova A.A.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/5929

Злокачественные новообразования желудка и пищеводно-желудочного перехода на продвинутых стадиях протекают доста- точно агрессивно, а перспективы лечения данных пациентов остаются малообещающими. Применение ингибиторов кон- трольных точек (checkpoint-inhibitors) зарекомендовало себя в качестве передового метода лечения различных видов рака во всем мире. В Российской Федерации препарат ниволумаб успешно прошел регистрацию в качестве монотерапии распро- страненного или рецидивирующего рака желудка или пищеводно-желудочного перехода после двух и более линий систем- ной противоопухолевой лекарственной терапии. Этот обзор литературы посвящен применению зарегистрированных ингиби- торов контрольных точек (ниволумаба, пембролизумаба, ипилимумаба) в качестве моно- и/или комбинированной терапии при опухолях желудка и пищеводно-желудочно перехода, включая опухоли с высокой микросателлитной нестабильностью (MSI- high). Данный обзор включает в себя описание основных терапевтических подходов с использованием ингибиторов кон- трольных точек: назначение их в монорежиме, в комбинации с другими ингибиторами контрольных точек (ипилимумабом) и цитотоксическими препаратами, а также в комбинации с ингибиторами тирозинкиназ (регорафенибом). Рассмотрены вопросы эффективности и переносимости данных комбинаций у пациентов в разных терапевтических линиях. Анализируется роль возможных предикторов ответа на терапию: оценены биомаркеры, такие как экспрессия PD-Ll, MSI, dMMR и TMB в опухоле- вых тканях, а также иммунофенотипирование в свежих образцах биопсии. Данная статья посвящена обзору и оценке сильных и слабых сторон применения ингибиторов контрольных точек и возможных вариантов их использования.

Malignant tumors of the stomach and esophagogastric junction in advanced stages progress quite aggressively, and the prospects for treatment of these patients remain unpromising. The use of checkpoint-inhibitors has proven to be an advanced treatment method for various types of cancer around the world. In theRussian Federation, nivolumab has been successfully registered as a monotherapy for common or recurrent stomach or esophagogastric junction cancer after two or more lines of systemic antitumor drug therapy. This literature review focuses on the use of registered checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab) as mono- and/or combined therapy in tumors of the stomach and esophagogastric junction, including tumors with high microsat- ellite instability (MSI-high). This review includes a description of the main therapeutic approaches using checkpoint inhibitors: prescription in mono-mode, in combination with other checkpoint inhibitors (ipilimumab) and cytotoxic drugs, and in combination with tyrosine kinase inhibitors (regorafenib). Issues of efficiency and tolerability of these combinations in patients in different therapeutic lines are considered. The role of possible predictors of therapy response is analyzed: biomarkers such as PD-Ll, MSI, dMMR and TMB expression in tumor tissues as well as immunofenotyping in fresh biopsy samples are evaluated. This article reviews and evaluates the strengths and weaknesses of checkpoint inhibitors and their possible uses.

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