medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-4S-8-15medsovet-6206Research ArticleИММУНОТЕРАПИЯ В ОНКОЛОГИИImmunotherapy in oncologyПервые результаты применения комбинированной терапии «атезолизумаб + бевацизумаб» у пациентов с распространенным гепатоцеллюлярным ракомPreliminary results of retrospective analysis Atezolizumab and Bevacizumab in first-line therapy of advanced HCChttps://orcid.org/0000-0002-6323-511XДжанянИ. А.DzhanyanI. А.

Джанян Ирина Анатольевна, врач-онколог отделения химиотерапии №17 Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова 

115478, Москва, Каширское шоссе, д. 24

Irina A.Dzhanyan, Oncologist of the Department of Chemotherapy № 17 of the Research Institute of Clinical Oncology named after N.N. Trapeznikov

24, Kashirskoye Shosse, Moscow, 115478

i-dzhanyan@mail.ruhttps://orcid.org/0000-0003-4244-7110НатрусоваМ. В.NatrusovaМ. V.

Натрусова Мария Витальевна, студент факультета фундаментальной медицины

119991, Москва, Ленинские горы, д. 1

Maria V. Natrusova, Student of the Department of Fundamental Medicine

1, Leninskie Gory, Moscow, 119991

maryvit14@gmail.comhttps://orcid.org/0000-0002-6244-4294БредерВ. В.BrederV. V.

Бредер Валерий Владимирович, д.м.н., ведущий научный сотрудник отделения химиотерапии №17 Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова

115478, Москва, Каширское шоссе, д. 24

Valeriy V. Breder, Dr. Sci. (Med.), Leading Researcher of the Department of Chemotherapy № 17 of the Research Institute of Clinical Oncology named after N.N. Trapeznikov

24, Kashirskoye Shosse, Moscow, 115478

vbreder@yandex.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationМосковский государственный университет имени М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian Federation20211206202104S815Copyright © Джанян И.А., Натрусова М.В., Бредер В.В., 20212021Джанян И.А., Натрусова М.В., Бредер В.В.Dzhanyan I.А., Natrusova М.V., Breder V.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/6206

Введение. Гепатоцеллюлярный рак (ГЦР) является актуальной проблемой современной онкологии. В РФ при подавляющем преобладании случаев распространенного опухолевого процесса показатель одногодичной летальности составляет 66%. В статье представлены первые результаты применения комбинированной терапии «атезолизумаб + бевацизумаб» при рас[1]пространенном ГЦР в первой линии лечения в рамках III фазы исследования IMbrave 150. Цель. Оценить эффективность и переносимость антиVEGF/PD-L1-терапии атезолизумабом в комбинации с бевацизумабом на примере 20 пациентов с неоперабельными формами ГЦР.Материалы и методы. Ретроспективно проанализирован опыт НМИЦ онкологии имени Н.Н. Блохина на примере 20 пациентов с распространенным ГЦР, получавших первую линию терапии атезолизумабом 1200 мг и бевацизумабом 15 мг/ кг 1 раз в 21 день до прогрессирования или до непереносимой токсичности, 11 пациентов из которых участвовали в глобальном открытом исследовании 3 фазы IMbrave15023,24 (NCT03434379/YO40245; Спонсор исследования F. Hoffmann-La Roche Ltd). Эффективность оценивалась по критериям RECICT 1.1. Анализ и визуализация данных проводились с использованием среды для статистических вычислений R 3.6.3 (R Foundation for Statistical Computing, Вена, Австрия). Описательные статистики для  количественных переменных представлены в виде среднего (стандартное отклонение) и медианы (1–3-й квартили), для категориальных – в виде абсолютного числа наблюдений (процент). Для сравнения количественных переменных (уровень АФП) в  динамике использовался тест Вилкоксона, различия считали статистически значимыми при p  < 0,05. Для оценки общей выживаемости и выживаемости до прогрессирования использовался метод Каплана – Майера.Результаты и обсуждение. Медиана наблюдения составила 9,3 мес. (1–3-й квартили: 6,0–14,4). Медиана ВДП составила 14,9 мес. (95% ДИ: 9,0 мес. – NE). Одногодичная выживаемость без прогрессирования для группы из 20 пациентов составила 56,2% (95% ДИ: 34,4–91,8%). Одногодичная ОВ для 20 составила 70,0% (95% ДИ: 49–100). Эффективность терапии: частичный ответ зарегистрирован у 3 (15,0%), стабилизация процесса (по REСIST 1.1) – у 13 (65,0%) пациентов, прогрессирование – у 4 (20,0%). Нежелательные явления 3-й степени выявлены у 7 из 20 пациентов (35%). Случаи артериальной гипертензии 3-й степени  отмечались у 20%; только у двух пациентов (10%) наблюдались аутоиммунные реакция (аутоиммунные панкреатит 2-й степе[1]ни длительностью 6 мес. и миозит 2-й степени длительностью 2 мес.). Также в нашем исследовании был один случай ослож[1]нения цирроза печени – кровотечения из варикозно расширенных вен пищевода 3-й степени.Вывод. Режим «атезолизумаб + бевацизумаб» показал высокую эффективность в первой линии терапии распространенного ГЦР.

Introduction

Introduction. HCC is a challenge for clinical oncology. 1-year mortality for advanced HCC accounts for 66% in the

Russian Federation

Russian Federation. The results obtained in the combined Atezolizumab and Bevacizumab therapy in the advanced HCC cases are reported.

Objective

Objective. To assess efficacy and safety of anti-VEGF/PD-L1 Atezolizumab plus Bevacizumab therapy in 20 unresectable HCC patients.

Materials and methods

Materials and methods. This analyses carried out in Blokhin National Cancer Research Centre included 20 patients with unresectable HCC treated with the first-line Atezolizumab (1200 mg) and Bevacizumab (15 mg/kg) once every 21 days, 11 patients participated into the global open-label phase 3 trial IMbrave150 23,24 (NCT03434379 / YO40245; Sponsor of study F. Hoffmann-La Roche, Ltd). The therapy was discontinued in cases of tumor progression or intolerant toxicity. The efficacy was evaluated according to RECICT 1.1 criteria. The results were analyzed and visualized on the basis of statistical calculations R 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics for quantitative variables are presented as mean (standard devia[1]tion) and median (lower and upper quartiles), for categorial variables as absolute number of observations (%). To compare quan[1]titative variables (AFP level) in progress Wilcoxon test was used. The differences were considered statistically significant with p < 0.05. Overall survival (OS) and progression-free survival (PFS) data were evaluated according to Kaplan-Meier methodology.

Results and discussion

Results and discussion. Median follow up was 9.3 months (quartile 1–3: 6.0–14.4) for 20 patients. Median progression free sur[1]vival was 14.9 months (lower bound, 95% CI, 9.0 months, upper bound NA). 12–month progression-free survival rate from the fixed date of the initial therapy was 56.2% (95% CI: 34.4–91.8%). One-year survival for 20 patients from the fixed date of the initial therapy was 70.0% (95% CI: 49–100). Treatment resulted in objective response (partial regression) in 3 (15%) pts, stable disease in 13 (65.0%) and progression in 4 (20.0%), patients. 35% of patients experienced Gr 3–4 adverse events with Gr3–4 arterial hypertension was the most common one in 20%. In 1 case esophageal varices hemorrhage Gr3 took place.

Conclusion

Conclusion. Atezolizumab and Bevacizumab seems to be highly efficient in advanced HCC.

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