Роль дурвалумаба в терапии опухолей желчевыводящих путей

Злокачественные новообразования желчевыводящих путей являются высокоагрессивными опухолями, с 5-летней выживаемостью при распространенных формах – не более 2–7%. В структуре заболеваемости злокачественными новообразованиями в РФ опухоли желчевывоводящих путей составляют около 2%. Долгое время терапевтические опции в данной локализации были крайне ограниченными. Неизменным стандартом первой линии терапии с 2010 г., основываясь на данных исследования ABC-02, являлась комбинация GemCis. Добавление анти-PD-L1-ингибитора дурвалумаба к цитостатическому дуплету GemCis, по данным рандомизированного двойного слепого плацебо-контролируемого исследования III фазы TOPAZ-1, впервые за двенадцать лет позволило обновить стандарт первой линии терапии распространенной формы аденокарциномы билиарного тракта, достигнув медианы выживаемости 12,9 мес. (11,6–14,1) в сравнении с 11,3 мес. (10,1–12,5) в группе плацебо (ОР 0,76 [0,64–0,91]). Частота объективного ответа составила 26,7% в группе дурвалумаба в сравнении с 18,7% в группе плацебо. Также было продемонстрировано, что медиана выживаемости сильно зависит от наилучшего достигнутого противоопухолевого ответа. Так, у пациентов в группе дурвалумаба с частичным/ полным ответом медиана выживаемости составила 19,5 мес. (95% ДИ: 15,7–28,3), при стабилизации заболевания – 13,6 мес. (95% ДИ: 12,2–14,7), а при прогрессировании заболевания – 5,7 мес. (95% ДИ: 3,6–8,9). В данной статье описаны особенности опухолевого микроокружения и иммуногенности холангиокарциномы, приведены исследования ранних фаз иммунотерапии дурвалумабом и тремелимумабом, выполнен подробный разбор ключевого исследования TOPAZ-1. Также в статье описан клинический случай, демонстрирующий продолжительный контроль рецидивной холангиокарциномы в течение 2 лет, благодаря существенным достижениям в терапии холангиокарциномы в виде внедрения иммунотерапии дурвалумабом, таргетной терапии ивосиденибом и применения новой методики локальной радиоэмболизации.

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