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

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.

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