
Журнал "Медицинский совет. Онкология" №10, 2019
DOI: https://doi.org/10.21518/2079-701X-2019-10-42-55
И.Б. Кононенко1, А.В. Снеговой1, В.Ю. Сельчук2 , 1 Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации, 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный медикостоматологический университет имени А.И. Евдокимова» Министерства здравоохранения Российской Федерации
Рак молочной железы (РМЖ) – наиболее распространенное в мире онкологическое заболевание. За последнее десятилетие научные достижения и новые способы лечения РМЖ значительно улучшили прогноз. Появление ингибиторов циклин-зависимой киназы (CDK) изменило парадигму лечения метастатического гормон-рецептор-положительного HER2 негативного (ГР+HER2-) РМЖ. За последние 4 года Управлением по контролю за продуктами и лекарствами США (FDA) одобрено три низкомолекулярных ингибитора CDK4/6 – рибоциклиб, палбоциклиб и абемациклиб. Изучение этих препаратов в комбинации с эндокринотерапией в рандомизированных клинических исследованиях MONALEESA, PALOMA и MONARCH продемонстрировало впечатляющие результаты у женщин с ГР+ HER2 негативным РМЖ в пре- или постменопаузе. В российские стандарты включено два низкомолекулярных ингибитора CDK4/6 – рибоциклиб и палбоциклиб. В этом обзоре представлены данные о клинической эффективности и токсичности, возникающей при использовании ингибиторов CDK4/6 с эндокринотерапией. Несмотря на схожий спектр токсичности, ингибиторы циклин-зависимых киназ отличаются по выраженности и некоторым видам нежелательных явлений. Практически все побочные эффекты, связанные с ингибиторами CDK 4/6, предсказуемы и быстро обратимы после приостановки терапии или редукции дозы препаратов. По мнению большинства экспертов, тщательное наблюдение за пациентом на фоне терапии ингибиторами CDK 4/6 позволяет своевременно провести коррекцию лечения и тем самым снизить риск тяжелых осложнений. Такой подход применялся во всех клинических исследованиях и рекомендован ведущими экспертными комиссиями для рутинной практики.
Cyclin-dependent kinase inhibitors: efficacy and safety
Inessa B. Kononenko1, Anton V. Snegovoi1, Vladimir Yu. Selchuk2,1 Federal State Budgetary Institution «Blokhin Russian Cancer Research Center» of the Ministry of Health of the Russian Federation, 2 Federal State Budgetary Educational Institution of the Higher Education «Moscow State University of Medicine and Dentistry named after A.I. Yevdokimov» of the Ministry of Healthcare of the Russian Federation
Breast Cancer is the most common type of cancer worldwide. Scientific advances and new ways of treating have significantly improved the prognosis of breast cancer in recent decades. The emergence of modern cyclin-dependent kinase (CDK) inhibitors has changed the treatment paradigm for metastatic hormone receptor (HR)-positive breast cancer. In the past four years, the CDK4/6 inhibitors, ribociclib, palbociclib and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)- positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA, MONALEESA and the MONARCH randomized clinical trials, respectively. In the Russian standards for the treatment of metastatic HR positive and HER2-negative breast cancer are included two inhibitors of CDK4/6 – ribociclib, palbociclib. This review summarizes the background of clinical efficacy and potential toxicities seen with the use CDK4/6 inhibitors with endocrine treatment in pre- or postmenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer. Despite the similar toxicities, inhibitors of cyclin-dependent kinases differ in their severity and some types of adverse events. Most hematologic abnormalities seen with CDK4/6 inhibitors are not complicated and are adequately managed with standard supportive care and dose adjustments when indicated. This review focuses on the practical management of adverse events associated with CDK4/6 inhibitors.
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