oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2023-22-1-35-42oncotomsk-2425Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESОпыт применения ингибитора поли (АДФ-рибозо) полимеразы олапариба в поддерживающей терапии BRCA-ассоциированного рака яичниковExperience in the use of olaparib poly (ADP-ribose) polymerase inhibitors in maintenance therapy of BRCA-associated ovarian cancerhttps://orcid.org/0000-0002-6927-3336ЖурманВ. Н.ZhurmanV. N.

Журман Варвара Николаевна, кандидат медицинских наук, врач-онколог, ГБУЗ «Приморский краевой онкологический диспансер»; ассистент кафедры акушерства и гинекологии, ФГБОУ ВО «Тихоокеанский государственный медицинский университет» Минздрава России

690105, г. Владивосток, ул. Русская, 59,

690002, г. Владивосток, пр. Острякова, 2

Varvara N. Zhurman, MD, PhD, Oncologist, Primorsky Regional Cancer Center; Assistant of the Department of Obstetrics and Gynecology, Pacific State Medical University of the Ministry of Health of Russia

59, Russkaya St., 690105, Vladivostok,

 22, Ostryakov Ave., 690002, Vladivostok

varvara2007@yandex.ruНечушкинаВ. М.NechushkinaV. M.

Нечушкина Валентина Михайловна, доктор медицинских наук, заместитель директора по научной работе и главный научный сотрудник, «Научно-образовательный центр «Евразийская онкологическая программа» EAFO» (г. Москва, Россия); профессор кафедры онкологии, лучевой терапии и лучевой диагностики, ФГБОУ ВО «Приволжский исследовательский медицинский университет», Минздрава России

125080, г. Москва, Волоколамское шоссе, 1, стр. 1,

603005, г. Нижний Новгород, пл. Минина и Пожарского, 10/1

Valentina M. Nechushkina, MD, DSc, Deputy Director for Research, Chief Researcher, Scientific and Educational Center “Eurasian Cancer Program” EAFO; Professor of the Department of Oncology, Radiation Therapy and Diagnostic Imaging, Privolzhsky Research Medical University of the Ministry of Health of Russia

1, Volokolamskoe sh., 125080, Moscow,

10/1, Minin and Pozharsky pl., 603005, Nizhny Novgorod

ГБУЗ «Приморский краевой онкологический диспансер»; ФГБОУ ВО «Тихоокеанский государственный медицинский университет» Минздрава РоссииРоссияPrimorsky Regional Cancer Center; Pacific State Medical University of the Ministry of Health of RussiaRussian Federation«Научно-образовательный центр «Евразийская онкологическая программа» EAFO»; ФГБОУ ВО «Приволжский исследовательский медицинский университет», Минздрава РоссииРоссияScientific and Educational Center “Eurasian Cancer Program” EAFO; Privolzhsky Research Medical University of the Ministry of Health of RussiaRussian Federation2023210220232213542Copyright © Журман В.Н., Нечушкина В.М., 20232023Журман В.Н., Нечушкина В.М.Zhurman V.N., Nechushkina V.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.siboncoj.ru/jour/article/view/2425

Цель исследования ‒ определить частоту мутаций генов BRCA1/2, эффективность лечения рака яичников в зависимости от их наличия и эффективность применения олапариба в поддерживающей терапии BRCA-ассоциированного рака яичников.

Материал и методы

Материал и методы. В ретроспективный анализ включено 355 пациенток с серозным раком яичников high-grade, I–IV стадий. Обследование на мутацию в гене BRCA1/2 выполнялось в рамках программы «Совершенствование молекулярно-генетической диагностики в Российской Федерации с целью повышения эффективности противоопухолевого лечения».

Результаты

Результаты. Мутации в генах BRCA1/2 выявлены у 98 из 355 (27,6 %) пациенток. Мутации гена BRCA1+ выявлены у 62 из 230 больных раком яичников IIIC–IV стадий (27,0 %), гена BRCA2 – у 9 из 230 (3,9 %). При раке яичников IIIС–IV стадий мутации генов BRCA отсутствовали у 159 из 230 (69,1 %) больных. Медиана времени до прогрессирования при IIIС–IV стадиях заболевания с мутацией в гене BRCA1 составила 22,0 мес, в гене BRCA2 – 27,0 мес, без мутаций в генах ВRCA1/2 – 17,0 мес, медиана продолжительности жизни – 70,0; 65,0 и 45,0 мес соответственно. Пациентки с серозной карциномой яичников high-grade I–IV стадий с мутацией в генах BRCA1/2 были разделены на две группы. Первую группу (6 из 26, 23,1 %) составили пациентки с серозной карциномой яичников high-grade IIIC–IV стадий, получавших олапариб в поддерживающем режиме после 1-й линии химиотерапии, вторую группу (20 из 26, 76,9 %) составили пациентки с серозной карциномой яичников high-grade I–IV стадий, получавшие олапариб в поддерживающем режиме после 2-й и более линий химиотерапии.

Заключение

Заключение. Наличие мутаций генов BRCA1/2 значимо увеличило медиану продолжительности жизни пациенток с серозным раком яичников IIIC–IV стадий, а выполнение первичной циторедукции значимо улучшало общую выживаемость и выживаемость до прогрессирования. Поддерживающая терапия олапарибом более целесообразна после 1-й линии лечения, нежели после последующих.

Aim to study the frequency of BRCA1/2 gene mutations , the efficacy of ovarian cancer therapy depending on the presence of BRCA1/2 mutations as well as the efficacy of olaparib maintenance therapy in BRCAassociated ovarian cancer.

Material and Methods

Material and Methods. The retrospective analysis included 355 patients with high-grade, stage I–IV serous ovarian cancer. The examination for a mutation in the BRCA1/2 gene was carried out within the framework of the program “Improvement of molecular genetic diagnostics in the Russian Federation in order to increase the effectiveness of antitumor treatment”.

Results

Results. Mutations in the BRCA1/2 genes were detected in 98 out of 355 (27.6 %) patients. Mutations of the BRCA1+ gene were detected in 62 out of 230 patients with ovarian cancer of stages IIIC–IV (27.0 %), the BRCA2 gene – in 9 out of 230 (3.9 %). In ovarian cancer of stages III–IV, BRCA gene mutations were absent in 159 of 230 (69.1 %) patients. The median time to progression in stages III–IV of the disease with a mutation in the BRCA1 gene was 22.0 months, in the BRCA2 gene – 27.0 months, in patients without mutations in the BRCA1/2 genes – 17.0 months, median life expectancy – 70.0; 65.0 and 45.0 months, respectively. Patients with serous ovarian carcinoma of high-grade I–IV stages with the presence of mutations in the BRCA1/2 genes were divided into two groups. The first group (6 out of 26 patients, 23.1 %) consisted of patients with stage IIIC–IV high-grade serous ovarian carcinoma, who received olaparib as maintenance therapy after the 1st line of chemotherapy, the second group (20 out of 26 patients, 76.9 %) were patients with stage I–IV high-grade serous ovarian carcinoma, who received olaparib in maintenance mode after 2 or more lines of chemotherapy.

Conclusion

Conclusion. The presence of BRCA1/2 gene mutations significantly increased the median life expectancy of patients with stage IIIC–IV serous ovarian cancer, and primary cytoreduction significantly improved both overall survival and survival to progression in this group of patients. Maintenance therapy with olaparib is more appropriate after the 1st line of treatment than after subsequent ones.

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