medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2025-543medsovet-9696Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSКомбинация капивасертиба и фулвестранта: новые возможности терапии HR+/HER2− метастатического рака молочной железыCapivasertib in combination with fulvestrant: New treatment options for HR+/HER2− metastatic breast cancerhttps://orcid.org/0000-0003-0092-0459КорниецкаяА. Л.KornietskayaA. L.

Корниецкая Анна Леонидовна - к.м.н., ведущий научный сотрудник отдела лекарственного лечения опухолей.

125284, Москва, 2-й Боткинский проезд, д. 3

Аnna L. Kornietskaya - Cand. Sci. (Med.), Leading Researcher of the Department of Drug Treatment of Tumors, Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Center.

3, 2nd Botkinskiy Proezd, Moscow, 125284

kornietskaya@mail.ruhttps://orcid.org/0000-0003-4879-2687БолотинаЛ. В.BolotinaL. V.

Болотина Лариса Владимировна - д.м.н., заведующая отделением химиотерапии.

125284, Москва, 2-й Боткинский проезд, д. 3

Larisa V. Bolotina - Dr. Sci. (Med.), Head of the Chemotherapy Department, Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Center.

3, 2nd Botkinskiy Proezd, Moscow, 125284

lbolotina@yandex.ruhttps://orcid.org/0000-0002-1993-3842ЕвдокимоваС. Ф.EvdokimovaS. F.

Евдокимова Сэвиндж Физулиевна - к.м.н., врач-онколог отделения химиотерапии.

125284, Москва, 2-й Боткинский проезд, д. 3

Sevindzh F. Evdokimova - Cand. Sci. (Med.), Oncologist of the Chemotherapy Department, Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Center.

3, 2nd Botkinskiy Proezd, Moscow, 125284

evdokimova.sevindzh@gmail.comhttps://orcid.org/0000-0002-6244-9159ПризоваН. С.PrizovaN. S.

Призова Наталия Сергеевна - к.м.н., врач-онколог отделения химиотерапии.

125284, Москва, 2-й Боткинский проезд, д. 3

Natalia S. Prizova - Cand. Sci. (Med.), Oncologist of the Chemotherapy Department, Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Center.

3, 2nd Botkinskiy Proezd, Moscow, 125284

sonrisa3n@mail.ruhttps://orcid.org/0000-0003-3196-1368КарагодинаЮ. Б.KaragodinaYu. B.

Карагодина Юлия Борисовна - научный сотрудник отдела лекарственного лечения опухолей.

125284, Москва, 2-й Боткинский проезд, д. 3

Yulia B. Karagodina - Researcher of the Department of Drug Treatment of Tumors, Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Center.

3, 2nd Botkinskiy Proezd, Moscow, 125284

yuliaborisovnakaragodina@gmail.comМосковский научно-исследовательский онкологический институт имени П.А. Герцена – филиал Национального медицинского исследовательского центра радиологииРоссияHertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological CenterRussian Federation2025010120260215259Copyright © Корниецкая А.Л., Болотина Л.В., Евдокимова С.Ф., Призова Н.С., Карагодина Ю.Б., 20262026Корниецкая А.Л., Болотина Л.В., Евдокимова С.Ф., Призова Н.С., Карагодина Ю.Б.Kornietskaya A.L., Bolotina L.V., Evdokimova S.F., Prizova N.S., Karagodina Y.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/9696

Идентификация и понимание роли различных сигнальных путей в патогенезе злокачественных новообразований, в частности рака молочной железы (РМЖ), существенно изменили ландшафт терапевтических возможностей данного заболевания. Как известно, гормон-рецептор положительный (HR+) HER2-негативный (HER2−) метастатический РМЖ (мРМЖ) является наиболее распространенным, но крайне гетерогенным с биологической точки зрения вариантом заболевания, что во многом определяет различия в ответе на эндокринотерапию. При этом у пациенток без висцерального криза эндокринная терапия является предпочтительным методом лечения, поскольку обладает большей активностью и лучшей переносимостью по сравнению с химиотерапией. Активация сигнального пути AKT стимулирует рост, пролиферацию и выживание опухолевых клеток, вызывая развитие резистентности к эндокринной терапии. Мутации PIK3CA, AKT и потеря PTEN являются наиболее частыми нарушениями, встречающимися примерно у 20–40% пациентов с ранним РМЖ и у 40% пациентов при метастатическом процессе. Будучи ингибитором AKT, блокирующим ключевую молекулу сигнального пути PIK3CA/ AKT/PTEN, капивасертиб продемонстрировал многообещающие результаты как в доклинических исследованиях, так и в клинических испытаниях в качестве монотерапии и в комбинации с фулвестрантом. Исследование FAKTION продемонстрировало эффективность и безопасность капивасертиба в сочетании с фулвестрантом, в первую очередь у пациентов с нарушениями сигнального пути PI3K/AKT/PTEN. Исследование Capitello-291 подтвердило полученные результаты, что позволило одобрить данную комбинацию для лечения HR+/HER2− РМЖ с альтерациями PIK3CA, AKT, PTEN. В настоящее время продолжаются клинические исследования по изучению эффективности капивасертиба, в том числе в первой линии терапии пациентов с HR+/HER2− мРМЖ с альтерациями сигнального пути PIK3CA/AKT/PTEN.

The identification and understanding of various signaling pathways involved in the pathogenesis of malignant neoplasms, particularly breast cancer (BC), have significantly transformed the therapeutic landscape of this disease. Hormone receptor-positive (HR+) HER2-negative (HER2−) metastatic BC (mBC) is the most common but biologically heterogeneous subtype, which largely accounts for the variability in response to endocrine therapy. In patients without visceral crisis, endocrine therapy remains the preferred treatment option due to its higher efficacy and better tolerability compared with chemotherapy. Activation of the AKT signaling pathway promotes tumor cell growth, proliferation, and survival, leading to the development of endocrine resistance. PIK3CA and AKT mutations, as well as PTEN loss, are among the most frequent alterations, occurring in approximately 20–40% of patients with early-stage BC and in up to 40% of those with metastatic disease. As an AKT inhibitor, capivasertib has shown promising results in both preclinical studies and clinical trials, either as monotherapy or in combination with fulvestrant. The FAKTION trial demonstrated the efficacy and safety of capivasertib combined with fulvestrant, particularly in patients with alterations in the PI3K/AKT/PTEN signaling pathway. The CAPItello-291 study confirmed these findings, leading to the approval of this combination for the treatment of HR+/HER2− breast cancer harboring PI3K/AKT/PTEN pathway alterations. Several clinical trials are currently underway to evaluate the efficacy of capivasertib, including that in the first-line treatment of patients with HR+/HER2− mBC harboring PI3K/AKT/PTEN pathway alterations.

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The authors declare that there are no conflicts of interest present.