Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press120910.17650/1994-4098-2024-20-1-64-81MAMMOLOGY. REVIEWSМАММОЛОГИЯ. ОБЗОРНЫЕ СТАТЬИEffectiveness of cyclin-dependent kinase 4 and 6 inhibitors for the treatment of hormonesensitive HER2-negative metastatic breast cancer in first-line therapy: A systematic literature reviewЭффективность ингибиторов циклинзависимых киназ 4 и 6 для лечения гормоночувствительного HER2-отрицательного метастатического рака молочной железы в первой линии терапии: систематический обзор литературыhttps://orcid.org/0000-0002-2686-1330AvxentyevN. A.АвксентьевН. А.
Russian Federation

Nikolay Aleksandrovich Avxentyev

3/2 Nastasyinsky Pereulok, Moscow 127006, Russia 

157/1 Volgogradskiy Prospekt, Moscow 109378, Russia

Николай Александрович Авксентьев 

127006 Москва, Настасьинский переулок, 3, стр. 2 

Россия, 109378 Москва, Волгоградский проспект, 157, корп. 1 

 

na@health-ma.ruAndreyashkinaI. I.АндреяшкинаИ. И.
Russian Federation

1/1 Novogireevskaya St., Moscow 111123, Russia 

Россия, 111123 Москва, Новогиреевская ул., 1, корп. 1 

https://orcid.org/0000-0001-7728-9533ArtamonovaE. V.АртамоноваЕ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522, Russia;

1 Ostrovityanova St., Moscow 117997, Russia;

61/2 Schepkina St., Moscow 129110, Russia 

Россия, 115522 Москва, Каширское шоссе, 24;

Россия, 117997 Москва, ул. Островитянова, 1;

Россия, 129110 Москва, ул. Щепкина, 61/2, корп. 1 

BolotinaL. V.БолотинаЛ. В.
Russian Federation

3 2-oy Botkinsky Proezd, Moscow 125284, Russia 

Россия, 125284 Москва, 2-й Боткинский проезд, 3 

KovalenkoE. I.КоваленкоЕ. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522, Russia 

Россия, 115522 Москва, Каширское шоссе, 24 

https://orcid.org/0000-0001-9130-2343SisiginaN. N.СисигинаН. Н.
Russian Federation

3/2 Nastasyinsky Pereulok, Moscow 127006, Russia 

Россия, 127006 Москва, Настасьинский переулок, 3, стр. 2

Financial Research Institute, Ministry of Finance of RussiaФГБУ «Научно-исследовательский финансовый институт» Минфина РоссииHealth and Market Access Consulting LLCООО «Хелс энд Маркет Аксесс Консалтинг»A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare DepartmentГБУЗ г. Москвы «Московский клинический научно-практический центр им. А.С. Логинова Департамента здравоохранения г. Москвы»N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииDepartment of Oncology and Radiotherapy, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russiaкафедра онкологии и лучевой терапии ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииDepartment of Oncology and Thoracic Surgery, M.F. Vladimirsky Moscow Regional Research and Clinical Instituteкафедра онкологии и торакальной хирургии ФДО ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского»P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Ministry of Health of RussiaМосковский научно-исследовательский онкологический институт им. П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России1905202420164810403202417052024https://ojrs.abvpress.ru/ojrs/article/view/1209

At present, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib, ribociclib, and abemaciclib are widely used for the first-line treatment of locally advanced or metastatic breast cancer. However, direct comparisons of these treatment options in randomized studies have not been conducted.

Aim of the work is to gather and analyze published data on the comparative effectiveness of CDK4/6 inhibitors in combination with aromatase inhibitors in postmenopausal patients with HR+/HER2– locally advanced or metastatic breast cancer. A systematic review of publications presenting results from original studies on the impact of CDK4/6 inhibitor therapy in combination with aromatase inhibitors on the survival of patients was performed. Nineteen studies with original data on progression-free survival and overall survival were identified. None of the studies found significant differences between different CDK4/6 inhibitors and aromatase inhibitors in terms of progression-free survival. A statistically significant superiority of ribociclib over palbociclib in terms of overall survival was observed in a single matching-adjusted indirect comparison, while seven other studies of various types (real-world data studies, matching-adjusted indirect comparisons, and meta-analyses) did not find significant differences between the investigated drugs in terms of overall survival.

Currently, there is no compelling evidence of the superiority of one CDK4/6 inhibitor over others. The decision on the preference for a specific drug within the class can only be made after conducting direct randomized comparison trials, or accumulating sufficient real-world data on the use of palbociclib, ribociclib, and abemaciclib.

В настоящее время для лечения местно-распространенного неоперабельного или метастатического рака молочной железы в первой линии терапии широко применяются ингибиторы циклинзависимых киназ 4 и 6 (CDK4/6): палбоциклиб, рибоциклиб и абемациклиб. Вместе с тем прямых сравнений данных вариантов лечения в рандомизированных исследованиях до сегодняшнего дня не проводилось.

Цель настоящей работы – сбор и анализ опубликованных данных по сравнительной эффективности применения ингибиторов CDK4/6 в комбинации с ингибиторами ароматазы у больных HR+/HER2– местно-распространенным или метастатическим раком молочной железы в постменопаузе.

Проведен систематический обзор публикаций, представляющих результаты оригинальных исследований влияния терапии ингибиторами CDK4/6 в комбинации с ингибиторами ароматазы на выживаемость больных. Обнаружено 19 работ, содержащих оригинальные данные о выживаемости без прогрессирования, общей выживаемости. Ни одно из исследований не обнаружило значимых различий между разными комбинациями ингибиторов CDK4/6 и ингибиторов ароматазы по показателю выживаемости без прогрессирования. Статистически значимое превосходство рибоциклиба над палбоциклибом по критерию общей выживаемости было получено в единственном скорректированном непрямом сравнении препаратов, тогда как 7 других работ различных типов (исследования на основе данных реальной клинической практики, скорректированные непрямые сравнения и метаанализы), проводивших сравнение ингибиторов CDK4/6 по данному критерию, значимых различий между исследуемыми препаратами не обнаружили.

В настоящее время отсутствуют убедительные свидетельства превосходства одного из ингибиторов CDK4/6 над другими. Решение о предпочтительности конкретного препарата класса может быть принято только после проведения сравнительных рандомизированных контролируемых исследований или накопления достаточного объема данных о применении палбоциклиба, рибоциклиба и абемациклиба в реальной клинической практике.

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