medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-9-62-72medsovet-5702Research ArticleГОРМОНОТЕРАПИЯHormonotherapyФулвестрант в лечении люминального метастатического рака молочной железы: баланс эффективности и безопасностиFulvestrant in the treatment of luminal metastatic breast cancer: the balance of effectiveness and safetyhttps://orcid.org/0000-0002-1836-0851КоролеваИ. А.KorolevaI. A.

Королева Ирина Альбертовна, д.м.н., профессор кафедры клинической медицины последипломного образования

443001, Самара, ул. Чапаевская, д. 227

Irina A. Koroleva, Dr. of Sci. (Med), Professor of the Department of clinical medicine of postgraduate education

227, Chapaevskaya St., Samara, 443001

korolevaia_samara@mail.ruhttps://orcid.org/0000-0002-2783-9493КоппМ. В.KoppM. V.

Копп Михаил Валериевич, д.м.н., врач-онколог многопрофильной клиники

443001, Самара, ул. Чапаевская, д. 227

Mikhail V. Kopp, Dr. of Sci. (Med), oncologist of the Multidisciplinary clinic

227, Chapaevskaya St., Samara, 443001

mvkopp@mail.ruМедицинский университет «Реавиз»РоссияMedical University “REAVIZ”Russian Federation202027072020096272Copyright © Королева И.А., Копп М.В., 20202020Королева И.А., Копп М.В.Koroleva I.A., Kopp M.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5702

В обзоре представлены результаты исследований фулвестранта при метастатическом раке молочной железы (мРМЖ). Гормонотерапия является эффективным методом лечения гормонопозитивного мРМЖ даже при наличии висцеральных метастазов, в отсутствие висцерального криза и без выявленной резистентности к эндокринотерапии. В период пандемии COVID-19 для больных гормонопозитивным мРМЖ гормонотерапия является более безопасной по сравнению с химиотерапией, т. к. не приводит к иммуносупрессии. Фулвестрант является «чистым антиэстрогеном», он обладает большим сродством к рецепторам эстрогенов, чем тамоксифен. Фулвестрант является одновременно конкурентным антагонистом и селективным деградатором рецепторов эстрогена (SERD), данный механизм действия обеспечивает полное блокирование эстрогенового сигнального пути. В исследовании III фазы CONFIRM была определена оптимальная доза фулвестранта – 500 мг 1 раз в 28 дней, нагрузочная доза – 500 мг в 15-й день 1-го мес. терапии. В исследовании III фазы FALCON (n = 462), в которое были включены больные мРМЖ в постменопаузе, ранее не получавшие никакой эндокринной терапии, сравнивался фулвестрант 500 мг с ингибитором ароматазы анастрозолом. Статистически значимое улучшение безрецидивной выживаемости (БРВ) было достигнуто при терапии фулвестрантом по сравнению с анастрозолом: 16,6 мес. в группе фулвестранта против 13,8 мес. при применении анастрозола (ОР 0,797; 95% ДИ 0,637–0,999; р = 0,0486). Подгрупповой анализ показал, что пациенты без висцеральных метастазов могут извлечь наибольшую пользу из приема фулвестранта. Во всех исследованиях фулвестрант 500 мг продемонстрировал хороший профиль токсичности, поэтому он изучается как компонент комбинированной гормонотерапии. В исследовании PALOMA-3 комбинация фулвестранта с палбоциклибом (ингибитор CDK4/6) продемонстрировала медиану ВБП 9,5 мес., монотерапия фулвестрантом – 4,6 мес. (ОР 0,46, p < 0,0001). В исследовании MONALEESA-3 медиана ВБП у пациенток, получавших рибоциклиб с фулвестрантом, по сравнению с теми, кто принимал плацебо с фулвестрантом, была значимо выше: 20,5 мес. и 12,8 мес. соответственно (ОР 0,593; 95% ДИ: 0,480–0,732; р < 0,001). В исследовании MONARCH-2 комбинация фулвестранта и абемациклиба изучалась во 2-й линии терапии, медиана ВБП составила 16,4 мес. в группе, получавшей фулвестрант и абемациклиб, и 9,3 мес. в группе фулвестранта и плацебо (ОР 0,553; 95% ДИ 0,449–0,681; p < 0,0001). Фулвестрант имеет удовлетворительный профиль переносимости, не требует сопроводительной терапии, входит в клинические рекомендации в монотерапии и комбинированной терапии.

The review presents the results of studies of fulvestrant in metastatic breast cancer (MBC). Hormone therapy is an effective method of treating hormone-positive metastatic breast cancer even in the presence of visceral metastases in the absence of a visceral crisis and without detected resistance to endocrine therapy. During the COVID-19 pandemic, hormone therapy is safer for patients with hormone-positive MBC than chemotherapy, since it does not lead to immunosuppression. Fulvestrant is a “pure antiestrogen”, it has a greater affinity for estrogen receptors than tamoxifen. Fulvestrant is both a competitive antagonist and a selective estrogen receptor degrader (SERD), this mechanism of action provides complete blocking of the estrogen signaling pathway. In the phase III CONFIRM study, the optimal dose of fulvestrate was determined to be 500 mg once every 28 days, with a loading dose of 500 mg on day 15 of the first month of therapy. In the FALCON phase III study (n = 462), which included postmenopausal MBC patients who had not previously received any endocrine therapy, fulvestrant 500 mg was compared with the aromatase inhibitor anastrozole. Significant improvement in PFS was achieved with fulvestrant therapy compared to anastrozole: 16.6 months in the fulvestrant group versus 13.8 months with anastrozole [OR = 0.797; 95% CI 0.637–0.999; p = 0.0486]. A subgroup analysis showed that patients without visceral metastases can benefit most from taking fulvestrant. In all studies fulvestrant 500 mg has demonstrated a good toxicity profile, so it is being studied as a component of combined endocrine therapy. In the PALOMA-3 study the combination of fulvestrant with palbociclib (CDK4/6 inhibitor) demonstrated a median PFS 9.5 months, compared with monotherapy with fulvestrant – 4.6 months (HR = 0.46, p < 0.0001). In the MONALEESA-3 study, the median PFS in patients receiving ribociclib with fulvestrant was significantly higher compared to those taking placebo with fulvestrant: 20.5 months and 12.8 months, respectively (HR = 0.593; 95% CI: 0.480–0.732; p < 0.001). In the MONARCH-2 study the combination of fulvestrant and abemaciclib was studied in the second line of therapy, the median PFS was 16.4 months in the group of fulvestrant and abemaciclib, and 9.3 months in the group of fulvestrant and placebo (HR = 0.553; 95% CI 0.449-0.681; p < 0.0001). Fulvestrant has a satisfactory toxicity profile, does not require supporting therapy, and is included in the clinical recommendations for monotherapy and combination therapy.

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