medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-9-42-47medsovet-6247Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSЭрлотиниб: как увеличить длительность эффективного применения ингибиторов тирозинкиназ при немелкоклеточном раке легкого с мутацией EGFRErlotinib: How to increase the duration of effective use of tyrosine kinase inhibitors in non-small cell lung cancer with EGFR mutationhttps://orcid.org/0000-0001-8907-1523БорисоваЕ. И.BorisovaE. I.

Борисова Елена Ивановна, кандидат медицинских наук, врач-онколог, отделение лекарственного лечения (химиотерапии) №4

115478, Москва, Каширское шоссе, д. 24

Elena I. Borisova, Cand. Sci. (Med.), Oncologist, Department of Drug Therapy (Chemotherapy) No. 4

24, Kashirskoye Shosse, Moscow, 115478

doctorborisova@yandex.ruhttps://orcid.org/0000-0001-5912-1155ГуторовС. Л.GutorovS. L.

Гуторов Сергей Львович, доктор медицинских наук, ведущий научный сотрудник, отделение лекарственного лечения (химиотерапии) №4

115478, Москва, Каширское шоссе, д. 24

Sergey L. Gutorov, Dr. Sci. (Med.), Leading Researcher, Department of Drug Therapy (Chemotherapy) No. 4

24, Kashirskoye Shosse, Moscow, 115478

s1gutorov@gmail.comНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian Federation202107082021094247Copyright © Борисова Е.И., Гуторов С.Л., 20212021Борисова Е.И., Гуторов С.Л.Borisova E.I., Gutorov S.L.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/6247

Ингибиторы тирозинкиназ 1–3-го поколения являются основным методом лечения при немелкоклеточном раке легкого с мутацией EGFR. При прогрессировании на фоне ингибиторов тирозинкиназ 1-го или 2-го поколения в первой линии примерно у 60% пациентов выявляется мутация Т790М. У таких пациентов возможно назначение осимертиниба во второй линии. Альтернативой является назначение осимертиниба в первой линии, но это ограничивает варианты последующего лечения, в связи с чем важной задачей является поиск стратегии, позволяющей максимально продлить эффективное лечение ингибиторами тирозинкиназ. Одним из рациональных подходов представляется применение комбинации ингибитора тирозинкиназ 1-го поколения с антиVEGF-агентами. В доступной литературе показано повышение эффективности при совместном применении эрлотиниба и антиангиогенных препаратов. Комбинация эрлотиниба и бевацизумаба, по данным ряда исследований, второй-третьей фазы привела к статистически значимому увеличению выживаемости без прогрессирования, однако не показала значимого увеличения общей выживаемости. В исследовании третьей фазы RELAY комбинация эрлотиниба и рамуцирумаба показала эффективность, сравнимую с применением осимертиниба в первой линии, однако результаты общей выживаемости пока недоступны. При этом открываются более широкие возможности выбора режима второй линии с учетом известной частоты выявления мутации T790M. Обсуждается попытка оптимизировать последовательность лечения, опцией которого является назначение комбинации эрлотиниба с бевацизумабом или рамуцирумабом в первой линии и осимертиниба во второй при наличии мутации T790M.

Tyrosine kinase inhibitors of the first, second and third generations are the main treatment method for non-small cell lung cancer with EGFR mutation. About 60% of patients progressing on a first-generation or second-generation tyrosine kinase inhibitor acquire T790M mutation. An alternative is first-line osimertinib, but second-line treatment options are limited, and therefore it is important to find a strategy that allows to extend the effective treatment of TKI. One of the rational approaches is the use of a combination of a first-generation tyrosine kinase inhibitor with anti-VEGF agents. The available information sources show an increase in the effectiveness of the combined use of erlotinib and antiangiogenic drugs-bevacizumab and ramucirumab. The combination of erlotinib and bevacizumab in several studies of the second — third phase, led to a statistically significant increase in progression-free survival, but did not show a significant increase in overall survival. In the Phase 3 RELAY study, the combination of erlotinib and ramucirumab showed comparable efficacy with the third-generation TKI — osimertinib in the first line, however, overall survival results are not yet available. At the same time, there are more opportunities to choose the secondline mode, taking into account the known frequency of detection of the T790M mutation. The optimal treatment sequence is discussed, with the option of prescribing a combination of erlotinib with bevacizumab or ramucirumab in the first line and osimertinib in the second in the presence of the T790M mutation. In such patients, osimertinib may be prescribed in the second line.

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