medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-545medsovet-8795Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONНемелкоклеточный рак легкого с мутацией в гене МЕТ: клинический случай лечения МЕТ-ингибитором капматинибомNon-small cell lung cancer with MET mutation: a clinical case of treatment with MET inhibitor capmatinibhttps://orcid.org/0000-0003-3734-2779МеньшиковК. В.MenshikovK. V.

Меньшиков Константин Викторович, к.м.н., доцент кафедры онкологии и клинической морфологии; врач-онколог отдела химиотерапии

450008, Уфа, ул. Ленина, д. 3

450054, Уфа, проспект Октября, д. 73/1

Konstantin V. Menshikov, Cand. Sci. (Med.), Associate Professor of the Department of Oncology and Clinical Morphological Sciences; Oncologist of the Chemotherapy Department

3, Lenin St., Ufa, 450008

73/1, Oktyabrya Ave., Ufa, 450054 

kmenshikov80@bk.ruhttps://orcid.org/0000-0003-0996-5995СултанбаевА. В.SultanbaevA. V.

Султанбаев Александр Валерьевич, к.м.н., доцент кафедры педагогики и психологии; заведующий отделом противоопухолевой лекарственной терапии

450008, Россия, Уфа, ул. Ленина, д. 3

450054, Россия, Уфа, проспект Октября, д. 73/1

Alexander V. Sultanbaev, Cand. Sci. (Med.), Associate Professor of the Department of Pedagogy and Psychology; Head of the Department of Antitumor Drug Therapy

3, Lenin St., Ufa, 450008

73/1, Oktyabrya Ave., Ufa, 450054

rkodrb@yandex.ruhttps://orcid.org/0000-0003-1185-977XМусинШ. И.MusinSh. I.

Мусин Шамиль Исмагилович, к.м.н., заведующий хирургическим отделением опухолей «голова – шея»

450054, Уфа, проспект Октября, д. 73/1

Shamil I. Musin, Cand. Sci. (Med.), Head of the Head & Neck Surgery Department

73/1, Oktyabrya Ave., Ufa, 450054

musin_shamil@mail.ruhttps://orcid.org/0000-0001-8779-4074ЧаловВ. С.ChalovV. S.

Чалов Виталий Сергеевич, заведующий отделением радиотерапии, врач-радиотерапевт

450054, Уфа, ул. Рихарда Зорге, д. 58, корп. 2 

Vitaliy S. Chalov, Head of the Department of Radiotheraphy

58/2, Richard Sorge St., Ufa, 450054 

v.chalov@pet-net.ruhttps://orcid.org/0000-0002-8665-8895МеньшиковаИ. А.MenshikovaI. A.

Меньшикова Ирина Асхатовна, к.м.н., доцент, доцент кафедры биологической химии

450008, Уфа, ул. Ленина, д. 3

Irina A. Menshikova, Cand. Sci. (Med.), Associate Professor, Associate Professor of the Department of Biological Chemistry

3, Lenin St., Ufa, 450008 

i-menshikova@bk.ruhttps://orcid.org/0000-0001-8340-7962НасретдиновА. Ф.NasretdinovA. F.

Насретдинов Айнур Фанутович, врач-онколог, заведующий отделением противоопухолевой лекарственной терапии №2

450054, Уфа, проспект Октября, д. 73/1

Ainur F. Nasretdinov, Oncologist, Head of the Department of Antitumor Drug Therapy No. 2

73/1, Oktyabrya Ave., Ufa, 450054

rkodrb@yandex.ruhttps://orcid.org/0000-0001-5926-0446СултанбаеваН. И.SultanbaevaN. I.

Султанбаева Надежда Ивановна, врач-онколог отделения противоопухолевой лекарственной терапии №1

450054, Россия, Уфа, проспект Октября, д. 73/1 

Nadezda I. Sultanbaeva, Oncologist of the Department of Antitumor Drug Therapy No. 1

73/1, Oktyabrya Ave., Ufa, 450054

nd.sultan@rambler.ruhttps://orcid.org/0000-0002-5871-5151ГалимовШ. Н.GalimovSh. N.

Галимов Шамиль Нариманович, д.м.н., профессор, заведующий кафедрой биологический химии

450008, Уфа, ул. Ленина, д. 3

Shamil N. Galimov, Dr. Sci. (Med.), Professor, Head of the Department of Biological Chemistry

3, Lenin St., Ufa, 450008

Башкирский государственный медицинский университет; Республиканский клинический онкологический диспансерРоссияBashkir State Medical University; Republican Clinical Oncology DispensaryRussian FederationРеспубликанский клинический онкологический диспансерРоссияRepublican Clinical Oncology DispensaryRussian FederationЦентр ядерной медицины «ПЭТ-Технолоджи»РоссияPET-Technology Nuclear Medicine CentreRussian FederationБашкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian Federation202423122024021146152Copyright © Меньшиков К.В., Султанбаев А.В., Мусин Ш.И., Чалов В.С., Меньшикова И.А., Насретдинов А.Ф., Султанбаева Н.И., Галимов Ш.Н., 20242024Меньшиков К.В., Султанбаев А.В., Мусин Ш.И., Чалов В.С., Меньшикова И.А., Насретдинов А.Ф., Султанбаева Н.И., Галимов Ш.Н.Menshikov K.V., Sultanbaev A.V., Musin S.I., Chalov V.S., Menshikova I.A., Nasretdinov A.F., Sultanbaeva N.I., Galimov S.N.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/8795

Ген MET кодирует клеточный рецептор, обладающий тирозинкиназной активностью и участвующий в процессах эмбрионального развития, органогенеза и заживления ран. При некоторых злокачественных новообразованиях, включая немелкоклеточный рак легкого, отмечается гиперэкспрессия гена МЕТ. Капматиниб является селективным MET-ингибитором Ib-типа. В исследование GEOMETRY-mono 1 был включен 151 пациент с делецией в 14-м экзоне гена MET. Для пациентов во второй линии терапии ЧОО составила 51%, медиана ВБП – 6,9 мес. Мы приводим клинический случай лечения НМРЛ у предлеченной пациентки в возрасте 50 лет с делецией в 14-м экзоне гена MET. Мутация в гене МЕТ выявлена при секвенировании нового поколения. Исходно пациентка обратилась на метастатической стадии заболевания, перенесла хирургический компонент лечения по поводу осложнения рака легкого. В первой линии получила платиносодержащий режим химиотерапии, при прогрессировании рассмотрена таргетная терапия. В настоящее время выживаемость без прогрессирования составляет 9 мес. Приведенное клиническое наблюдение демонстрирует эффективность таргетной терапии капматинибом у предлеченной пациентки с распространенным НМРЛ с делецией в 14-м экзоне гена МЕТ. Необходимость тестирования пациентов с распространенным неплоскоклеточным немелкоклеточным раком легкого на редкие мутации, такие как МЕТ, RET, очевидна.

The MET gene encodes cell surface receptors that have tyrosine kinase activity and mediates embryonic development, organogenesis, and wound healing. Overexpression of MET is observed in some human cancers, including non-small cell lung cancer. Capmatinib is a selective type Ib inhibitor of MET. A total of 151 patients with MET exon 14 skipping mutations were enrolled in the GEOMETRY-mono 1 study. ORR achieved was 51% in patients receiving second-line chemotherapy, the median PFS was 6.9 months. We present a clinical case of NSCLC treatment in a pretreated patient aged 50 years with MET exon 14 skipping mutations. The MET mutation was detected by next-generation sequencing. Initially, the patient presented with metastatic disease, underwent surgical treatment due to lung cancer complications. She received a platinum-containing chemotherapy regimen as the first-line therapy, and in case of progression, targeted therapy was considered. Currently, progression-free survival is 9 months. This clinical observation shows the efficacy of targeted capmatinib therapy in a pretreated patient with advanced NSCLC and MET exon 14 skipping mutations. Testing of patients with advanced non-squamous non-small cell lung cancer for rare mutations such as MET, RET is clearly needed.

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J Clin Oncol. 2016;34(7):721-730. https://doi.org/10.1200/JCO.2015.63.4600.Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P et al. MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. J Clin Oncol. 2016;34(7):721-730. https://doi.org/10.1200/JCO.2015.63.4600.Spigel DR, Edelman MJ, O’Byrne K, Paz-Ares L, Mocci S, Phan S et al. Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non-Small-Cell Lung Cancer: METLung. J Clin Oncol. 2017;35(4):412-420. https://doi.org/10.1200/JCO.2016.69.2160.Spigel DR, Edelman MJ, O’Byrne K, Paz-Ares L, Mocci S, Phan S et al. Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non-Small-Cell Lung Cancer: METLung. 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The authors declare that there are no conflicts of interest present.