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Абемациклиб как оригинальный представитель циклин-зависимых киназ в лечении люминального HER2-негативного диссеминированного рака молочной железы

https://doi.org/10.21518/2079-701X-2020-9-27-42

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Аннотация

Ингибиторы циклин-зависимых киназ 4 и 6 (CDK4/6) – палбоциклиб, рибоциклиб и абемациклиб – стали новым стандартом лечения больных гормонорецепторопозитивным HER2-негативным диссеминированным или метастатическим раком молочной железы (ГР + HER2 МРМЖ) вне зависимости от линии терапии, менопаузального статуса и других индивидуальных характеристик. Кратковременное торможение CDK4/6 приводит к обратимой остановке клеточного цикла в фазе G1 с восстановлением фосфорилирования Rb-1 и полного клеточного цикла после прекращения ингибиции. Несмотря на сходный механизм действия, изложенный в статье, препараты обладают индивидуальными характеристиками. Абемациклиб, отличаясь от палбоциклиба и рибоциклиба по химической структуре, обладает более выраженной избирательностью к CDK4, меньшим миелосупрессивным действием, что позволяет принимать его непрерывно, более выраженной липофильностью, активнее взаимодействует с АТФ, вследствие чего может взаимодействовать и с другими киназами. Абемациклиб, единственный из всех ингибиторов CDK4/6, оказался эффективным при рефрактерном ГР + HER2 МРМЖ: объективный эффект (ОЭ) зарегистрирован у 19,7%, контроль заболевания – у 42,4% больных, медиана выживаемости без прогрессирования (ВБП) составила 5,95 мес., медиана общей выживаемости (ОВ) – 22,32 мес. Комбинация абемациклиба с фулвестрантом во 2-й линии лечения повышает эффективность лечения по сравнению с одной эндокринотерапией (ЭТ): медиану ВБП – с 9,3 до 16,9 мес. (р < 0,001), ОЭ – с 16 до 35% (р < 0,001) в ITT-популяции, медиану ОВ – с 37,3 до 46,7 мес. (p  = 0,01) для комбинации абемациклиба с фулвестрантом. Применение абемациклиба с нестероидными ингибиторами ароматазы (НСАИ) по сравнению с одними ингибиторами ароматазы (АИ) в 1-й линии лечения приводит к увеличению медианы ВБП с 14,76 до 28,18 мес. (p = 0,000002) и повышению ОЭ с 37 до 49,7% (р = 0,005) в ITT-популяции. Доминирующим побочным эффектом абемациклиба является диарея, регистрируемая в 82–90% случаев, не превышающая 3-й степени тяжести, частота последней не превышает 13%, диарея обратима, купируется антидиарейными препаратами. Комбинация ЭТ с абемациклибом дает возможность повысить эффективность лечения у наиболее прогностически неблагоприятного контингента больных.

Об авторе

Н. С. Бесова
Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина
Россия

Бесова Наталия Сергеевна, к.м.н., ведущий научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) № 1 научно-исследовательского института клинической онкологии им. академика РАН и РАМН Н.Н. Трапезникова

115478, Москва, Каширское шоссе, д. 24



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Для цитирования:


Бесова Н.С. Абемациклиб как оригинальный представитель циклин-зависимых киназ в лечении люминального HER2-негативного диссеминированного рака молочной железы. Медицинский Совет. 2020;(9):27-42. https://doi.org/10.21518/2079-701X-2020-9-27-42

For citation:


Besova N.S. Abemaciclib as an original inhibitor of cyclin-dependent kinase for the treatment of luminal HER2-negative disseminated breast cancer. Meditsinskiy sovet = Medical Council. 2020;(9):27-42. (In Russ.) https://doi.org/10.21518/2079-701X-2020-9-27-42

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ISSN 2079-701X (Print)
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