medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-228medsovet-8358Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSОсобенности лекарственного лечения пациентов с немелкоклеточным раком легкого с мутацией EGFR L858R в 21-м экзонеThe therapeutic features of EGFR L858R exon 21 mutation in non-small cell lung cancerhttps://orcid.org/0000-0001-7879-614XМандринаМ. О.MandrinaM. O.

Мандрина Марьяна Олеговна - аспирант онкологического отделения лекарственных методов лечения (химиотерапевтическое) №3.

115478, Москва, Каширское шоссе, д. 24

Maryana O. Mandrina - Postgraduate Student of Department of Antitumor Drug Therapy No. 3.

24, Kashirskoye Shosse, Moscow, 115478

minavasya@yandex.ruhttps://orcid.org/0000-0002-4548-1026БарболинаТ. Д.BarbolinaT. D.

Барболина Татьяна Дмитриевна - к.м.н., врач-онколог, научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтическое) №3, НМИЦО имени Н.Н. Блохина; ассистент кафедры онкологии лечебного факультета НОИ «Высшая школа клинической медицины имени Н.А. Семашко», РосУниМед.

115478, Москва, Каширское шоссе, д. 24; 127473, Москва, ул. Делегатская, д. 20, стр. 1

Tatyana D. Barbolina - Cand. Sci. (Med.), Oncologist, Researcher, Department of Antitumor Drug Therapy No. 3, Blokhin NMRCO; Assistant, Department of Oncology, Medical Faculty, Scientific and Educational Institute “Higher School of Clinical Medicine named after N.A. Semashko”, ROSUNIMED.

24, Kashirskoye Shosse, Moscow, 115478; 20, Bldg. 1, Delegatskaya St., Moscow, 127473

Katan4ik@list.ruhttps://orcid.org/0000-0002-4822-5044ВладимироваЛ. Ю.VladimirovaL. Yu.

Владимирова Любовь Юрьевна - д.м.н., профессор, заведующая отделом лекарственного лечения опухолей, заведующая отделением противоопухолевой лекарственной терапии.

344037, Ростов-на-Дону, ул. 14-я линия, д. 6

Liubov Y. Vladimirova  -Dr. Sci. (Med.), Professor, Head of the Department of Drug Treatment of Tumors, Head of the Department of Antitumor Drug Therapy.

63, 14th Liniya St., Rostov-on-Don, 344037

https://orcid.org/0000-0003-0965-0264СторожаковаА. Э.StorozhakovaA. E.

Сторожакова Анна Эдуардовна - к.м.н., врач-онколог отделения противоопухолевой лекарственной терапии.

344037, Ростов-на-Дону, ул. 14-я линия, д. 6

Anna E. Storozhakova - Cand. Sci. (Med.), Oncologist of the Department of Antitumor Drug Therapy.

63, 14th Liniya St., Rostov-on-Don, 344037

https://orcid.org/0000-0003-4469-502XЛактионовК. К.LaktionovK. K.

Лактионов Константин Константинович - д.м.н., первый заместитель директора, заведующий онкологическим отделением лекарственных методов лечения (химиотерапевтическое) №3, НМИЦО имени Н.Н. Блохина; исполняющий обязанности заведующего кафедрой онкологии и лучевой терапии лечебного факультета, профессор кафедры онкологии и лучевой терапии лечебного факультета, РНИИМУ имени Н.И. Пирогова.

115478, Москва, Каширское шоссе, д. 24; 117997, Москва, ул. Островитянова, д. 1

Konstantin K. Laktionov - Dr. Sci. (Med.), First Deputy Director, Head of Department of Antitumor Drug Therapy No. 3, Blokhin NMRCO; Acting Head of the Department of Oncology and Radiation Therapy of the Medical Faculty, Professor of the Department of Oncology and Radiation Therapy of the Medical Faculty, Pirogov RNRMU.

24, Kashirskoye Shosse, Moscow, 115478; 1, Ostrovityanov St., Moscow, 117997

lkoskos@mail.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. Блохина; Российский университет медицины (РосУниМед)РоссияBlokhin National Medical Research Center of Oncology; Russian University of Medicine (ROSUNIMED)Russian FederationНациональный медицинский исследовательский центр онкологииРоссияNational Medical Research Center of OncologyRussian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. Блохина; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияBlokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical UniversityRussian Federation2024230720240105459Copyright © Мандрина М.О., Барболина Т.Д., Владимирова Л.Ю., Сторожакова А.Э., Лактионов К.К., 20242024Мандрина М.О., Барболина Т.Д., Владимирова Л.Ю., Сторожакова А.Э., Лактионов К.К.Mandrina M.O., Barbolina T.D., Vladimirova L.Y., Storozhakova A.E., Laktionov K.K.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/8358Введение

Введение. Монотерапия ингибиторами тирозинкиназы (ИТК) EGFR приводит к худшему прогнозу для пациентов с мутацией 21-го экзона L858R, чем для пациентов с экзоном 19 Del. Таким образом, поиск альтернативных лекарственных стратегий, улучшающих результаты лечения пациентов, имеющих НМРЛ с мутацией L858R, является актуальной проблемой. В данной статье представлены предварительные результаты экспериментального исследования эффективности химиотерапии, интегрированной в таргетную антиEGFR-терапию пациентов с немелкоклеточным раком легкого (НМРЛ) с мутацией в 21-м экзоне гена EGFR.

Цель

Цель. Улучшить результаты выживаемости без прогрессирования I линии терапии пациентов, имеющих НМРЛ с мутацией L858R.

Материалы и методы

Материалы и методы. С 2015 по 2021 г. в исследование включено 23 пациента с метастатическим НМРЛ с мутацией L858R в 21-м экзоне для I линии лечения. Пациенты получали первые 2 мес. терапию ингибиторами тирозинкиназы с последующим прекращением приема таргетных препаратов и получением 3 курсов химиотерапии по схеме «паклитаксел и карбоплатин». Далее возобновлялась таргетная терапия до прогрессирования заболевания. Период наблюдения составил 36 мес.

Результаты

Результаты.

Частота объективного ответа (ЧОО) составила 59,1%. Медиана выживаемости без прогрессирования – 23 мес. [95% ДИ: 16–36]. У 4 (18,1%) пациентов развилась токсичность 3–4-й степени на фоне химиотерапии, в связи с чем у одного пациента был отменен 3-й курс химиотерапии. Из-за токсичности на фоне таргетной терапии у 1 пациента выполнена редукция дозы гефитиниба и у 1 пациента произошла смена препарата с гефитиниба на афатиниб.

Выводы

Выводы. Предварительные результаты нашего исследования показали, что интегрирование химиотерапии в таргетное лечение данной категории пациентов может стать новой достойной опцией, позволяющей увеличить медиану ВБП.

Introduction

Introduction. Monotherapy with EGFR tyrosine kinase inhibitors (TKIs) results in a worse prognosis for patients with the exon 21 L858R mutation than for patients with exon 19 Del. Thus, the search for alternative drug strategies that improve treatment outcomes for patients with NSCLC with the L858R mutation is an urgent problem. This article presents preliminary results of a pilot study of the effectiveness of chemotherapy integrated into targeted anti-EGFR therapy for patients with non-small cell lung cancer (NSCLC) with a mutation in exon 21 of the EGFR gene.

Aim

Aim. To improve progression-free survival results on first-line therapy in patients with NSCLC with the L858R mutation.

Materials and methods

Materials and methods. From 2015 to 2021 23 patients were included in the study with advanced L858R 21 exon mutation NSCLC for the first line of treatment. Patients received TKI therapy for the first 2 months, followed by discontinuation of targeted therapy and receiving 3 courses of paclitaxel and carboplatin. Target therapy was then resumed until disease progression. The follow up period was 36 months.

Results

Results. The objective response rate (ORR) was 59.1%. Median progression-free survival 23 months [95% CI: 16–36]. Four (18.1%) patients developed grade 3-4 toxicity during chemotherapy, and therefore the 3rd course of chemotherapy was canceled in one patient. Due to toxicity during targeted therapy, gefitinib dose was reduced in one patient and the drug was changed from gefitinib to afatinib in the other one patient.

Conclusion

Conclusion. Preliminary results of our study showed that integrating chemotherapy into targeted treatment for this category of patients may become a new worthy option to increase median PFS.

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