tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2020-10-2-3tumors-740Research ArticleОБЗОРЫ И АНАЛИТИКАREVIEWS AND ANALYSISНеобходимо ли добавлять антиангиогенную терапию к химиотерапии у пациентов с метастатическим раком толстой кишки и мутацией в гене BRAF? Результаты систематического обзора и мета-анализаIs it necessary to add anti-angiogenic therapy to chemotherapy in patients with metastatic colorectal cancer and BRAF mutation? The systematic review and meta-analysis resultsФедянинМ. Ю.FedyaninM. Yu.

Михаил Ю. Федянин, д. м. н., старший научный сотрудник онкологического отделения лекарственного лечения (химиотерапевтического) №2, кафедра онкологии и гематологии 

Москва

Mikhail Yu. Fedyanin, MD, PhD, DSc, Senior Researcher, Oncology Department of Drug Therapy (Chemotherapy) No. 2, Department of Oncology and Hematology

Moscow

fedianinmu@mail.ruПолянскаяЕ. М.PolyanskayaE. M.

Елизавета М. Полянская, аспирант онкологического отделения лекарственного лечения (химиотерапевтического) № 2

Москва

Polyanskaya M. Elizaveta, Postgraduate Student Breast Cancer Department of Drug Therapy (Chemotherapy) No. 2

Moscow

lazimira@mail.ruЕльснукаеваХ.Х. М.Elsnukaeva H. H M.

Хеда Х.-М. Эльснукаева, аспирант онкологического отделения лекарственного лечения (химиотерапевтического) № 2

Москва

Heda H.‑M. Elsnukaeva, Postgraduate Student Breast Cancer Department of Drug Therapy (Chemotherapy) No. 2

Moscow

elsnukaeva1992@mail.ruТрякинА. А.TryakinA. A.

Алексей А. Трякин, д. м. н., главный научный сотрудник онкологического отделения лекарственного лечения (химиотерапевтического) №2, заведующий отделением дневного стационара по онкологическому профилю, доцент кафедры онкологии с курсами онкологии и патологической анатомии

Уфа

Alexey A. Tryakin, MD, PhD, DSc, Chief Researcher, Oncology Department of Drug Therapy (Chemotherapy) No. 2,Day Hospital,  Associate Professor of the Department of Oncology with courses oncology and pathological anatomy

Ufa

atryakin@mail.ruПокатаевИ. А.PokataevI. А.

Илья А. Покатаев, к. м. н., руководитель центра химиотерапии

Москва

Ilia A. Pokataev, MD, PhD, Head of the Chemotherapy Center

Moscow

pokia@mail.ruИгнатоваЕ. О.Ignatova Е. О.

Екатерина О. Игнатова, к. м. н., научный сотрудник онкологического отделения лекарственного лечения (химиотерапевтического) №2

Москва

 

Ekaterina O. Ignatova, MD, PhD, Researcher at Department, Oncology Department of Drug Therapy (Chemotherapy) No. 2

Moscow

md.ignatova@gmail.comСергеевЮ. С.Sergeev U. S.

Юрий С. Сергеев, к. м. н, доцент кафедры онкологии института клинической медицины

Москва

Urii S. Sergeev, MD, PhD, Associate Professor, Department of Oncology, Institute of Clinical Medicine

Moscow

БулановА. А.BulanovA. A.

Анатолий А. Буланов, д. м. н., старший научный сотрудник онкологического отделения лекарственного лечения (химиотерапевтического) №2

Москва

Anatoly A. Bulanov, MD, PhD, DSc, Senior Researcher, Oncology Department of Drug Therapy (Chemotherapy) No. 2

Moscow

a_bulanov@mail.ruТюляндинС. А.Tjulandin S. A.

Сергей А. Тюляндин, проф., д. м. н., заведующий онкологическим отделением лекарственного лечения (химиотерапевтического) №2 

Москва

Sergei A. Tjulandin, MD, PhD, DSc, Prof., Head of the Oncology Department, of Drug Therapy (Chemotherapy) No. 2

Moscow

stjulandin@gmail.comФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России; ФНМО «Российский университет дружбы народов»РоссияN. N. Blokhin National Medical Research Center of Oncology; Peoples» Friendship University of RussiaRussian FederationФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииRussian FederationN. N. Blokhin National Medical Research Center of OncologyRussian FederationФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России; ГБУЗ «Московский Клинический Научный Центр имени А.С. Логинова ДЗМ», ИДПО «Башкирский государственный медицинский университет»Russian FederationN. N. Blokhin National Medical Research Center of Oncology; A. S. Loginov Moscow Clinical Scientific Center of the Department of Health of the City of Moscow; Bashkir State Medical UniversityRussian FederationГБУЗ «Городская клиническая онкологическая больница №1» ДЗМRussian FederationCity Clinical Oncological Hospital № 1Russian FederationФГАУО ВО Первый МГМУ им И.М. Сеченова Минздрава РоссииRussian FederationI. M. Sechenov First Moscow State Medical UniversityRussian Federation2020311220201023644Copyright © Федянин М.Ю., Полянская Е.М., Ельснукаева Х.М., Трякин А.А., Покатаев И.А., Игнатова Е.О., Сергеев Ю.С., Буланов А.А., Тюляндин С.А., 20202020Федянин М.Ю., Полянская Е.М., Ельснукаева Х.М., Трякин А.А., Покатаев И.А., Игнатова Е.О., Сергеев Ю.С., Буланов А.А., Тюляндин С.А.Fedyanin M.Y., Polyanskaya E.M., Elsnukaeva  H.M., Tryakin A.A., Pokataev I.А., Ignatova  Е.О., Sergeev  U.S., Bulanov A.A., Tjulandin  S.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.malignanttumors.org/jour/article/view/740Введение

Введение. Антиангиогенные таргетные препараты являются неотъемлемым компонентом системной терапии метастатического рака толстой кишки. Однако к настоящему времени не было проведено ни одного проспективного исследования, которое бы напрямую отвечало на вопрос о необходимости добавления антиангиогенных препаратов к химиотерапии при метастатическом раке толстой кишки с мутацией в гене BRAF. Мы провели систематический обзор и мета-анализ по оценке эффективности добавления антиангиогенной терапии к химиотерапии у пациентов с метастатическим раком толстой кишки с мутацией в гене BRAF.

Материалы и методы

Материалы и методы. Проведен поиск статей и тезисов в базах данных PubMed, ASCO и ESMO, опубликованных до сентября 2020 года и содержащих информацию о результатах проспективных рандомизированных исследований по сравнению комбинации анти-ангиогенных препаратов (бевацизумаба, афлиберцепта или рамуцирумаба) в первой или во второй линии терапии метастатического рака толстой кишки, в которых указана эффективность в зависимости от наличия мутаций в гене BRAF. Первичным критерием эффективности явилось отношение рисков прогрессирования или смерти (ОР) с 95% доверительным интервалом (95% ДИ). Мета-анализ проведен с помощью программы Review Manager версии. 5.3.

Результаты

Результаты. 4 исследования соответствовали критериям отбора (AVF2107 g, AGITG MAX, VELOUR и RAISE), которые включили данные 120 пациентов с мутацией BRAF, 65 (54%) больным проводилась комбинация химиотерапии с антиангиогенным препаратом и 55 (46%) пациентам — только химиотерапия. По результатам мета-анализа отмечено улучшение выживаемости без прогрессирования (ОР 0,64, 95% ДИ 0,4–1,02; p = 0,06; I 2 = 0 %, p для гетерогенности 0,7; 3 исследования) и общей выживаемости (ОР 0,51, 95% ДИ 0,32–0,82; p = 0,005; I 2 = 0 %, p для гетерогенности 0,54; 4 исследования) в группе с антиангиогенными препаратами.

Выводы

Выводы. Комбинация химиотерапии с антиангиогенными препаратами в первой или во второй линии терапии улучшает выживаемость без прогрессирования и общую выживаемость у больных с метастатическим раком толстой кишки и мутацией в гене BRAF. Необходимо проведение проспективных рандомизированных исследований в данной популяции больных для определения оптимального режима лечения первой линии.

Introduction

Introduction: targeted anti‑angiogenic drugs are the integral component of systemic therapy for metastatic colorectal cancer. To date, there have been no prospective studies that would directly answer the question of the need to add anti‑ angiogenic agents to chemotherapy for BRAF‑mutated metastatic colorectal cancer. We performed a systematic review and meta‑analysis to evaluate the efficacy of adding anti‑angiogenic therapy to chemotherapy in patients with metastatic colorectal cancer harboring a mutation in the BRAF gene.

Materials and methods

Materials and methods: We searched for articles and abstracts in the PubMed, ASCO and ESMO databases, published before September 2020 and containing information on the results of prospective randomized trials comparing the combination of anti‑angiogenic agents (bevacizumab, aflibercept or ramucirumab) in the first‑or second‑line therapy for metastatic colorectal cancer, which indicate the efficacy depending on the presence of mutations in the BRAF gene. The primary endpoint was the risk ratio (RR) for progression or death with a 95 % confidence interval (95 % CI). The meta‑analysis was carried out using the Review Manager, version 5.3.

Results

Results: 4 studies met the selection criteria (AVF2107 g, AGITG MAX, VELOR and RAISE), which included data from 120 patients with the BRAF mutation, 65 (54 %) patients received a combination of chemotherapy with an anti‑angiogenic agent, and 55 (46 %) patients received only chemotherapy. The meta‑analysis showed improved progression‑free survival (RR 0.64, 95 % CI 0.4–1.02; p = 0.06; I 2 = 0 %, p for heterogeneity = 0.7; 3 studies) and overall survival (RR 0.51, 95 % CI 0.32–0.82; p = 0.005; I 2 = 0 %, p for heterogeneity = 0.54; 4 studies) in the group treated with anti‑angiogenic agents.

Conclusions

Conclusions: the combination of chemotherapy with anti‑angiogenic agents in the first‑or second‑line therapy improves progression‑free survival and overall survival in patients with BRAF‑mutated metastatic colorectal cancer. Prospective randomized trials in this patient population are needed to determine the optimal first‑line treatment regimen.

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