akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2026.769akusherstvo-2884Research ArticleREVIEW ARTICLEНАУЧНЫЙ ОБЗОРClinical significance and safety profile of antibody-drug conjugates in malignancies of the female reproductive systemКлиническое значение и профиль безопасности антитело-лекарственных конъюгатов при злокачественных новообразованиях женской репродуктивной системыhttps://orcid.org/0009-0005-7021-4906УзденоваД. М.UzdenovaD. M.

Узденова Джамиля Муратовна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Dzhamilya M. Uzdenova

29 Nakhichevansky Lane, Rostov-on-Don 344022

dzhami.uzd00@gmail.comhttps://orcid.org/0009-0000-1313-6378ТимофееваЕ. А.TimofeevaE. A.

Тимофеева Елизавета Андреевна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Elizaveta A. Timofeeva

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0006-8352-5081ИсаевД. М.IsaevD. M.

Исаев Дмитрий Максимович

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Dmitriy M. Isaev

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0005-1152-5106МестоеваЗ. Б.MestoevaZ. B.

Местоева Зарина Беслановна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Zarina B. Mestoeva

29 Nakhichevansky Lane, Rostov-on-Don 344022

ЕвсиковаЕ. Р.EvsikovaE. R.

Евсикова Екатерина Романовна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Ekaterina R. Evsikova

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0008-3064-7549КузнецоваА. А.KuznetsovaA. A.

Кузнецова Анна Андреевна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Anna A. Kuznetsova

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0004-8409-8005ЗабелинН. В.ZabelinN. V.

Забелин Никита Витальевич

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Nikita V. Zabelin

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0000-9559-0071КоваленкоЮ. В.KovalenkoYu. V.

Коваленко Юлия Витальевна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Yulia V. Kovalenko

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0003-6534-5114КузнецовД. С.KuznetsovD. S.

Кузнецов Данил Сергеевич

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Danil S. Kuznetsov

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0008-2308-8064БембееваА. Е.BembeevaA. E.

Бембеева Александра Евгеньевна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Alexandra E. Bembeeva

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0005-9381-9756МонидК. А.MonidK. A.

Монид Кирилл Андреевич

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Kirill A. Monid

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0002-7470-8047КолеухоА. В.KoleukhoA. V.

Колеухо Анастасия Витальевна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Anastasiya V. Koleukho

29 Nakhichevansky Lane, Rostov-on-Don 344022

https://orcid.org/0009-0005-9137-9873ГильУ. М.GilU. M.

Гиль Ульяна Михайловна

344022 Ростов-на-Дону, Нахичеванский переулок, д. 29

Ulyana M. Gil

29 Nakhichevansky Lane, Rostov-on-Don 344022

ФГБОУ ВО «Ростовский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияRostov State Medical University, Ministry of Health of the Russian FederationRussian Federation20262107202600Online First2884Copyright © Uzdenova D.M., Timofeeva E.A., Isaev D.M., Mestoeva Z.B., Evsikova E.R., Kuznetsova A.A., Zabelin N.V., Kovalenko Y.V., Kuznetsov D.S., Bembeeva A.E., Monid K.A., Koleukho A.V., Gil U.M., 20262026Узденова Д.М., Тимофеева Е.А., Исаев Д.М., Местоева З.Б., Евсикова Е.Р., Кузнецова А.А., Забелин Н.В., Коваленко Ю.В., Кузнецов Д.С., Бембеева А.Е., Монид К.А., Колеухо А.В., Гиль У.М.Uzdenova D.M., Timofeeva E.A., Isaev D.M., Mestoeva Z.B., Evsikova E.R., Kuznetsova A.A., Zabelin N.V., Kovalenko Y.V., Kuznetsov D.S., Bembeeva A.E., Monid K.A., Koleukho A.V., Gil U.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/2884Introduction

Introduction. Antibody-drug conjugates (ADCs) are expanding the therapeutic landscape of systemic treatment for malignancies of the female reproductive system, particularly in the setting of disease progression following standard chemotherapy. Their efficacy is determined by tumor target expression, antibody structure, cytotoxic payload, and drug-to-antibody ratio. However, increased selectivity of delivery does not reduce the risk of systemic and organ-specific toxicity, including adverse events affecting various organs.

Aim

Aim: to synthesize data on the clinical significance and safety profile of ADCs currently used or under investigation in ovarian, endometrial, and cervical cancer, with an analysis of the frequency, clinical manifestations, mechanisms, prevention, and management of adverse events.

Materials and Methods

Materials and Methods. An analytical review of publications on ADCs in gynecologic oncology was conducted, including phase I–III randomized trials, reviews, clinical guidelines, and supportive care documents. Agents targeting folate receptor alpha (FRα), tissue factor (TF), human epidermal growth factor receptor 2 (HER2), trophoblast cell surface antigen 2 (Trop-2), and cadherin-6 were analyzed. The analysis included data on molecular characteristics of the agents, antitumor activity, adverse event frequency, grade ≥ 3 toxicity, organ-specific complications, and safety monitoring approaches.

Results

Results. The most clinically significant ADCs in gynecologic oncology are mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan; promising data have also been identified for Trop-2- and cadherin-6-targeting conjugates. Mirvetuximab soravtansine is characterized by a predominance of ocular complications, largely unrelated to FRα expression in the cornea. Tisotumab vedotin is associated with ocular toxicity, hemorrhagic complications, and peripheral neuropathy, related to tissue factor expression and microtubule-inhibiting payload. For trastuzumab  deruxtecan,  the  most  significant  toxicities  are  gastrointestinal  toxicity, myelosuppression, cardiotoxicity, and drug-induced pneumonitis. Trop-2-directed ADCs are more frequently associated with mucositis, myelosuppression, gastrointestinal disorders, and alopecia. The safety profile of each agent is determined not only by the target but also by the type of cytotoxic payload and dosing regimen.

Conclusion

Conclusion. ADCs occupy an important position in the treatment of malignancies of the female reproductive system; however, their safe use requires individualized risk assessment, patient education, multidisciplinary monitoring, and timely dose modification. Further research should focus on identifying predictors of toxicity, optimizing preventive measures, and developing personalized ADC regimens.

Введение

Введение. Антитело-лекарственные конъюгаты (АЛК) расширяют возможности системной терапии злокачественных новообразований женской репродуктивной системы, особенно при прогрессировании заболевания после стандартной химиотерапии. Их эффективность определяется экспрессией опухолевой мишени, структурой антитела, цитотоксической нагрузкой и отношением количества лекарственного вещества к антителу. Вместе с тем повышение избирательности доставки не снижает риск системной и органоспецифической токсичности, включая нежелательные явления со стороны различных органов.

Цель

Цель: обобщить данные о клиническом значении и профиле безопасности АЛК, применяемых или изучаемых при раке яичников, эндометрия и шейки матки, с анализом частоты, клинических проявлений, механизмов развития, профилактики и коррекции нежелательных явлений.

Материалы и методы

Материалы и методы. Проведен аналитический обзор публикаций, посвященных АЛК в онкогинекологии, включая рандомизированные исследования I–III фаз, обзоры, клинические рекомендации и документы по поддерживающей терапии. Проанализированы препараты, нацеленные на фолатный рецептор альфа (англ. folate receptor alpha, FRα), тканевой фактор (англ. tissue factor, TF), рецептор эпидермального фактора роста человека 2-го типа (англ. human epidermal growth factor receptor 2, HER2), трофобластический антиген клеточной поверхности 2-го типа (англ. trophoblast cell surface antigen 2, Trop-2) и кадгерин-6. В анализ включены сведения о молекулярной характеристике препаратов, противоопухолевой активности, частоте нежелательных явлений, токсичности ≥ 3-й степени, органоспецифических осложнениях и подходах к мониторингу безопасности.

Результаты

Результаты. Наиболее клинически значимыми АЛК в онкогинекологии являются мирветуксимаб соравтанзин, тизотумаб ведотин и трастузумаб дерукстекан, перспективные данные выявлены также для Trop-2- и кадгерин-6-направленных конъюгатов. Мирветуксимаб соравтанзин характеризуется преобладанием офтальмологических осложнений, преимущественно не связанных с экспрессией FRα в роговице. Тизотумаб ведотин ассоциирован с офтальмотоксичностью, геморрагическими осложнениями и периферической нейропатией, что связано с экспрессией тканевого фактора и микротубул-ингибирующей нагрузкой. Для трастузумаба дерукстекана наиболее значимыми являются гастроинтестинальная токсичность, миелосупрессия, кардиотоксичность и лекарственный пневмонит. Trop-2-направленные АЛК чаще сопровождаются мукозитом, миелосупрессией, гастроинтестинальными нарушениями и алопецией. Профиль безопасности каждого препарата определяется не только мишенью, но и типом цитотоксической нагрузки и режимом дозирования.

Заключение

Заключение. АЛК занимают важное место в терапии злокачественных опухолей женской репродуктивной системы, при этом их безопасное применение требует предварительной оценки индивидуального риска, информирования пациенток, междисциплинарного мониторинга и своевременной модификации дозы. Дальнейшие исследования должны быть направлены на уточнение предикторов токсичности, оптимизацию профилактических мероприятий и разработку персонализированных режимов применения АЛК.

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