Рибоциклиб + гормонотерапия в адъювантном режиме при раннем раке молочной железы: профилактика рецидивов. Новые возможности

Огнерубов Н. А. Рибоциклиб + гормонотерапия в адъювантном режиме при раннем раке молочной железы: профилактика рецидивов. Новые возможности. Современная Онкология. 2023;25(4):432–439.
DOI: 10.26442/18151434.2023.4.202548

© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.

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Ognerubov NA. Ribociclib + adjuvant hormone therapy in early breast cancer: prevention of recurrence. New opportunities. A review. Journal of Modern Oncology. 2023;25(4):432–439.
DOI: 10.26442/18151434.2023.4.202548

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Аннотация

Рак молочной железы (РМЖ) занимает лидирующее положение среди всех злокачественных новообразований у женщин во всем мире и 4‑е место по смертности. Большинство случаев диагностируют на I–III стадиях. Среди молекулярно-биологических вариантов преобладает люминальный HER2 отрицательный (HER2-), составляющий 70–75%. В настоящее время методы лечения, сочетающие хирургическое вмешательство с химио- и, несколько реже, лучевой терапией, с последующей адъювантной гормонотерапией на протяжении до 10 лет, являются стандартной опцией при РМЖ. Реализация стандарта преследует профилактику раннего рецидива у пациентов в группе высокого риска с первично гормонорезистентной опухолью. Тем не менее по окончании лечения он развивается у 27–57% больных РМЖ II–III стадий. Для их профилактики при раннем HR положительном (HR+) HER2- РМЖ применяют инновационный класс лекарственных препаратов – ингибиторы циклинзависимых киназ 4/6 – в комбинации с гормонотерапией (ингибиторы ароматазы, антиэстрогены, агонисты гонадотропин-рилизинг-гормона), чему и посвящено рандомизированное исследование III фазы NATALEE, оценивающее эффективность и безопасность рибоциклиба в сочетании с эндокринной терапией при раннем неметастатическом РМЖ. В нем принимали участие больные РМЖ II–III стадий, в том числе с N0. Пациентам исследовательской группы назначали рибоциклиб в дозе 400 мг/сут в течение 21 дня в комбинации с ингибиторами ароматазы, а в контроле – только ингибиторы ароматазы. Медиана наблюдения – 34 мес. Трехлетняя выживаемость без инвазивного заболевания составила в группе рибоциклиба 90,7%, у лиц контроля – 87,6%. Риск отдаленного метастазирования и инвазивных заболеваний снижался на 25,1% в группе рибоциклиба. Соответственно, рибоциклиб продемонстрировал тенденцию к улучшению общей выживаемости. Начальная доза 400 мг/сут позволила снизить частоту нежелательных явлений, среди которых преобладают нейтропения (62,5%), артралгия (37,3%) и печеночная токсичность (26,4%). Самыми частыми причинами досрочного прекращения приема рибоциклиба стали печеночная токсичность (8,9%) и артралгия (1,3%). Полученные результаты демонстрируют статистически и клинически превосходящую эффективность применения рибоциклиба в комбинации с гормонотерапией при лечении раннего HR+ HER2- РМЖ с высоким риском развития рецидива.

Ключевые слова: ранний рак молочной железы, рецидив, профилактика, ингибиторы CDK4/6, рибоциклиб, ингибиторы ароматазы

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Breast cancer (BC) occupies a leading position among all malignant neoplasms in women worldwide and is the 4th deadliest. Most cases are diagnosed in stages I–III. Among the molecular biological variants, luminal HER2 negative (HER2-) prevails, accounting for 70–75%. Currently, therapies combining surgery with chemotherapy and, more rarely, radiation therapy, followed by adjuvant hormone therapy for up to 10 years, are a standard of care in BC. The goal of these regimens is the prevention of early recurrence in patients in the high-risk group with a primary hormone-resistant tumor. However, at the end of treatment, it occurs in 27–57% of patients with stage II–III breast cancer. For its prevention in early HR-positive (HR+) HER2- BC, an innovative class of drugs, cyclin-dependent kinase 4/6 inhibitors, is used combined with hormone therapy (aromatase inhibitors, anti-estrogens, gonadotropin-releasing hormone agonists), which is the subject of a randomized phase III NATALEE study evaluating the efficacy and safety of ribociclib in combination with endocrine therapy in early non-metastatic BC. The study enrolled patients with stage II–III breast cancer, including those with N0. Patients of the study group received ribociclib at a dose of 400 mg/day for 21 days in combination with aromatase inhibitors, and in the control group, only aromatase inhibitors. The median follow-up was 34 months. Three-year survival without invasive disease was 90.7% in the ribociclib group and 87.6% in controls. The risk of distant metastasis and invasive diseases was reduced by 25.1% in the ribociclib group. Therefore, ribociclib tended to improve overall survival. The initial dose of 400 mg/day reduced the incidence of adverse events; the most common were neutropenia (62.5%), arthralgia (37.3%) and hepatic toxicity (26.4%). The most common reasons for discontinuing ribociclib were hepatic toxicity (8.9%) and arthralgia (1.3%). The results demonstrate a statistical and clinical superiority of ribociclib in combination with hormone therapy in the treatment of early HR+ HER2- breast cancer with a high risk of recurrence.

Keywords: early breast cancer, relapse, prevention, CDK4/6 inhibitors, ribociclib, aromatase inhibitors

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Авторы

Н. А. Огнерубов*

Пензенский институт усовершенствования врачей – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Пенза, Россия
*ognerubov_n.a@mail.ru

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Nikolai A. Ognerubov*

Penza Institute for Advanced Training of Physicians – branch of the Russian Medical Academy of Continuous Professional Education, Penza, Russia
*ognerubov_n.a@mail.ru

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