Фулвестрант в терапии люминального HER2-негативного метастатического рака молочной железы

Гормонотерапия является эффективным методом лечения люминального HER2-негативного метастатического РМЖ (мРМЖ). Ингибиторы ароматазы и фулвестрант – основные препараты гормонотерапии. Фулвестрант является одновременно конкурентным антагонистом и селективным деградатором рецепторов эстрогена (SERD). В исследовании III фазы FALCON (n = 462), в которое были включены больные мРМЖ в постменопаузе, ранее не получавшие никакой эндокринной терапии, сравнивался фулвестрант с ингибитором ароматазы анастрозолом. Статистически значимое улучшение 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 фулвестрант проявил наибольшую эффективность у пациентов без висцеральных метастазов. Во всех исследованиях фулвестрант продемонстрировал хороший профиль токсичности, именно поэтому он изучается как компонент комбинированной гормонотерапии. В исследовании PALOMA-3 комбинация фулвестранта с палбоциклибом (ингибитор CDK4/6) показала медиану ВБП 9,5 мес. по сравнению с монотерапией фулвестрантом – 4,6 мес. (ОР = 0,46, p < 0,0001 В исследовании MONALEESA-3 у пациенток, получавших рибоциклиб с фулвестрантом, медиана ВБП была значимо выше по сравнению с теми, кто принимал плацебо с фулвестрантом: 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 второй линии терапии: медиана ВБП составила 16,4 мес. в группе пациенток, получавших фулвестрант и абемациклиб, и 9,3 мес. – в группе фулвестранта и плацебо (ОР = 0,553; 95% ДИ: 0,449–0,681; p < 0,0001). Исследование SOLAR-1 продемонстрировало эффективность комбинации «фулвестрант + алпелисиб» (ингибитор PI3K) при люминальном HER2-негативном мРМЖ, ассоциированном с мутацией PIK3CA в I и II линиях терапии. Медиана ВБП в группе «фулвестрант + алпелисиб» составила 11 мес. по сравнению с 5,7 мес.  в группе фулвестранта (ОР = 0,65; 95% ДИ: 0,50–0,85; р < 0,001). На основании данных клинических исследований можно говорить о том, что комбинация ингибиторов ароматазы с ингибиторами CDK4/6 является оптимальной первой линией лечения у больных с гормоночувствительными опухолями, т. е. при прогрессировании более 1 года после окончания адъювантной гормонотерапии. В свою очередь, фулвестрант ± ингибиторы CDK4/6 применяются при прогрессировании болезни на фоне адъювантной гормонотерапии в первой линии или в качестве второй линии при прогрессировании на терапии ингибиторами ароматазы по поводу метастатического рака. Комбинация «фулвестрант + алпелисиб» является высокоэффективной во второй линии терапии люминальнго HER2-негативного мРМЖ при наличии мутации PIK3CA.

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