medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-20-75-82medsovet-6583Research ArticleТАРГЕТНАЯ ТЕРАПИЯ ОПУХОЛЕЙTarget therapy of tumorsТаргетная терапия люминального HER2-негативного метастатического рака молочной железы c мутацией PIK3CA: комбинация алпелисиба с фулвестрантом в реальной клинической практикеTarget therapy of luminal HER2-negative advanced breast cancer with PIK3CA mutation: combination of alpelisib plus fulvestrant in real clinical practicehttps://orcid.org/0000-0002-7224-3111ФилоненкоД. А.FilonenkoD. A.

к.м.н., заведующая дневным стационаром по онкологическому профилю, 

111123, Москва, шоссе Энтузиастов, д. 86

Cand. Sci. (Med.), Head of  the  Day Hospital for  Oncological Profile, 

86, Entuziastov Shosse, Moscow, 111123

shubina_d@mail.ruhttps://orcid.org/0000-0002-2745-9765ИбрагимоваТ. М.IbragimovaT. M.

врач-онколог дневного стационара по  онкологическому профилю, 

111123, Москва, шоссе Энтузиастов, д. 86

Oncologist, Day Hospital for  Oncological Profile,

86, Entuziastov Shosse, Moscow, 111123

tansylu.ibragim@gmail.comhttps://orcid.org/0000-0001-5417-0425ПольшинаН. И.PolshinaN. I.

врач-онколог дневного стационара по  онкологическому профилю, 

111123, Москва, шоссе Энтузиастов, д. 86

Oncologist, Day Hospital for Oncological Profile, 

86, Entuziastov Shosse, Moscow, 111123

dr.polshina@yandex.ruhttps://orcid.org/0000-0001-7299-8744БелогуроваА. В.BelogurovaA. V.

врач-онколог дневного стационара по онкологическому профилю, 

111123, Москва, шоссе Энтузиастов, д. 86

Oncologist, Day Hospital for Oncological Profile, 

86, Entuziastov Shosse, Moscow, 111123

belogurova.avl@yandex.ruhttps://orcid.org/0000-0002-0259-117XХатьковаЕ. И.KhatkovaE. I.

врач-онколог дневного стационара по  онкологическому профилю, 

111123, Москва, шоссе Энтузиастов, д. 86

Oncologist, Day Hospital for  Oncological Profile,

86, Entuziastov Shosse, Moscow, 111123

khatkovae@gmail.comhttps://orcid.org/0000-0003-0551-7810АрутюнянЭ. А.ArutiunianE. A.

врач-онколог дневного стационара по  онкологическому профилю, 

111123, Москва, шоссе Энтузиастов, д. 86

Oncologist, Day Hospital for  Oncological Profile,

86, Entuziastov Shosse, Moscow, 111123

a.arutynyan@mknc.ruhttps://orcid.org/0000-0003-3717-1148ВолковаЕ. И.VolkovaE. I.

врач-эндокринолог клинико-диагностического отделения, 

111123, Москва, шоссе Энтузиастов, д. 86

Endocrinologist, Clinical Diagnostic Department, 

86, Entuziastov Shosse, Moscow, 111123

volkowa_endocrinology@mail.ruhttps://orcid.org/0000-0003-4848-6938ЖуковаЛ. Г.ZhukovaL. G.

д.м.н., заместитель директора по онкологии, 

111123, Москва, шоссе Энтузиастов, д. 86

Dr. Sci. (Med.), Deputy Director for Oncology,

86, Entuziastov Shosse, Moscow, 111123

zhukova.lyudmila008@gmail.comМосковский клинический научный центр имени А.С. ЛогиноваРоссияLoginov Moscow Clinical Scientific CenterRussian Federation2021101220210207582Copyright © Филоненко Д.А., Ибрагимова Т.М., Польшина Н.И., Белогурова А.В., Хатькова Е.И., Арутюнян Э.А., Волкова Е.И., Жукова Л.Г., 20212021Филоненко Д.А., Ибрагимова Т.М., Польшина Н.И., Белогурова А.В., Хатькова Е.И., Арутюнян Э.А., Волкова Е.И., Жукова Л.Г.Filonenko D.A., Ibragimova T.M., Polshina N.I., Belogurova A.V., Khatkova E.I., Arutiunian E.A., Volkova E.I., Zhukova L.G.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/6583Введение

Введение. Комбинация алпелисиба с фулвестрантом одобрена к применению у пациенток с гормонопозитивным (ГР+) HER2- негативным (HER2–) метастатическим раком молочной железы (мРМЖ) с мутацией PIK3CA после прогрессирования на фоне гормонотерапии. Данные об эффективности алпелисиба у предлеченных пациенток, получавших и химио-, и гормонотерапию, ограничены только результатами, полученными в исследовании I фазы. Нами представлен собственный опыт применения алпелисиба у 19 пациенток после предшествующей гормоно- и химиотерапии.

Цель

Цель. Оценить эффективность и переносимость алпелисиба в комбинации с фулвестрантом у пациенток ГР+ HER2– мРМЖ с мутацией PIK3CA в реальной клинической практике в ранних и поздних линиях лечения.

Материалы и методы

Материалы и методы. У пациенток с ГР+ HER2– мРМЖ с мутацией PIK3CA изучалась комбинация алпелисиба 300 мг/сут per os и фулвестранта 500 мг внутримышечно в 1-й, 15-й и 28-й день, далее каждые 28 дней. Терапия проводилась до прогрессирования заболевания или непереносимой токсичности.

Результаты

Результаты. С февраля по октябрь 2021 г. в Московском клиническом научном центре имени А.С. Логинова 19 пациенток с ГР+ HER2– мРМЖ с мутацией PIK3CA получили терапию в режиме «алпелисиб + фулвестрант». Медиана предшествующих линий лечения составила 5, в т. ч. все 19 (100%) пациенток получили терапию ингибиторами CDK4/6, 14 (74%) – фулвестрантом и (или) эверолимусом и 15 (79%) – химиотерапию. У 4 (21%) пациенток алпелисиб применялся в качестве 2-й линии, у остальных 15 (79%) – в более поздних линиях лечения. Медиана времени без прогрессирования составила 7 мес. Эффект лечения оценен у 18 из 19 пациенток, частичная регрессия достигнута у 5 (28%) пациенток, стабилизация болезни – у 9 (50%), прогрессирование болезни  – у  4  (22%). Наиболее частыми нежелательными явлениями были: гипергликемия  – у  74%, в т. ч. 3-й степени у 4 (22%) пациенток, повышение креатинина – у 42% (1-й и 2-й степени) и сыпь – у 37%, в т. ч. 3-й степени у 4 (22%). Только одна пациентка прекратила терапию в связи с отеком Квинке.

Выводы

Выводы. Алпелисиб в комбинации с фулвестрантом эффективен как в ранних, так и в поздних линиях лечения при ГР+ HER2– мРМЖ с мутацией PIK3CA, в т. ч. после применения фулвестранта, ингибиторов CDK4/6 и (или) эверолимуса. 

Introduction

Introduction. Сombination of alpelisib plus fulvestrant is approved in patients with hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer (ABC) after progression on hormonotherapy. Efficacy data of alpelisib in heavily pretreated patients with HR+/HER-2-, PIK3CA-mutated advanced breast cancer are limited, only results from phase I trial are available. Here we report our results of alpelisib efficacy in 19 heavily pretreated patients.

Object

Object: to evaluate efficacy and safety of combination alpelisib plus fulvestrant in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer in initial and later lines of therapy in real clinical practice.

Materials and methods

Materials and methods. Combination of  alpelisib plus fulvestrant was investigated in  19  patients with HR+/HER2-, PIK3CAmutated ABC, alpelisib at a dose of 300 mg per day plus fulvestrant at a dose of 500 mg i.m. every 28 days and once on day 15. Treatment continued until disease progression or unacceptable toxicity.

Results

Results. From February 2021 19 patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer were treated with alpelisib plus fulvestrant. The data cut off is October 2021. Median lines of treatment in advanced disease was five, including 19 (100%) patients received CDK4/6, 14 (74%) – fulvestrant and/or everolimus and 15 (79%) – chemotherapy. 4 (21%) received alpelisib in a second line, 15 (79%) – in subsequent lines. Median progression-free survival was 7 months. The response was evaluated in 18 patients: partial response was achieved in 5 (28%) patients, stable disease – in 9 (50%), disease progression – 4 (22%). The most frequent adverse events were hyperglycemia – 74% (grade 3 – 22%), creatinine increased – 42% and rash – 37% (grade 3 – 22%). Only one patient has discontinued the treatment due to Quincke`s edema.

Conclusions

Conclusions. Combination of alpelisib with fulvestrant is an effective option both in initial and later lines of therapy in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer including fulvestrant, CDK4/6 inhibitors and/or everolimus – pretreated patients. 

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