Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press76010.17650/1726-9776-2017-13-4-16-24LECTUREЛЕКЦИЯImmunotherapy in urothelial cancer: recent data and perspectivesИммунотерапия уротелиального рака: реалии и перспективыVolkovaM. I.ВолковаМ. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

Мария Игоревна Волкова.

115478 Москва, Каширское шоссе, 24

mivolkova@rambler.ruGridnevaYa. V.ГридневаЯ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24 

Ol’shanskayaA. S.ОльшанскаяА. С.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24 

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России3012201713416241501201815012018https://oncourology.abvpress.ru/oncur/article/view/760

Immune-checkpoint inhibitors blocking the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) have shown a prominent anti-tumor activity with long-term responses and an acceptable toxicity profile  in clinical trials. Pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab are anti-PD-1/PD-L1 agents that redefine the standard of care for advanced urothelial carcinoma. CTLA-4 inhibitors are also under investigation in this setting. Phase III trial KEYNOTE-045 has demonstrated significant survival benefit in patients treated with pembrolizumab comparing with the standard second-line chemotherapy. Atezolizumab, nivolumab, avelumab, and durvalumab were also recommended for platinum-pretreated urothelial carcinoma patients based on phase II data. Following investigations of biomarkers such as PD-L1 expression are needed to determine high-responders to immunotherapy. This review article describes the advances in immunotherapy with immune-checkpoint inhibitors.

У больных уротелиальным раком ингибиторы контрольных точек, блокирующие такие звенья пути передачи иммунного сигнала, как рецептор программируемой смерти 1 (PD-1), его лиганд 1-го типа (PD–L1) и антиген цитотоксического лимфоцита 4 (CTLA-4) в рамках клинических испытаний продемонстрировали существенную противоопухолевую активность, высокую длительность ответов, а также приемлемый профиль токсичности. Недавно разработанные ингибиторы PD-1 – пембролизумаб и ниволумаб, а также ингибиторы PD–L1 – атезолизумаб, авелумаб и дурвалумаб – уже заставили пересмотреть существующие стандарты системной терапии уротелиального рака. Блокаторы CTLA-4 также исследуются при данном виде опухоли. Результаты исследования III фазы KEYNOTE-045 показали убедительное преимущество показателей общей выживаемости у больных резистентным уротелиальным раком, получавших пембролизумаб, по сравнению со стандартной химиотерапией 2-й линии. Атезолизумаб, ниволумаб, авелумаб и дурвалумаб также рекомендованы для лечения цисплатин-рефрактерных опухолей на основании результатов исследований II фазы. В 1-й линии терапии уротелиального рака у пациентов с противопоказаниями к назначению цисплатина доказана активность пембролизумаба и атезолизумаба. Актуальным является изучение биомаркеров, способных выделить когорту пациентов, имеющих высокий шанс ответа на иммунотерапию. Настоящий обзор представляет данные исследований, посвященных системной иммунотерапии уротелиального рака.

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