medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2025-501medsovet-9698Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSЭффективность таргетной терапии у пациентов с распространенным немелкоклеточным раком легкого с редкими мутациями гена EGFR и сочетаниями мутацийEfficacy of targeted therapy in advanced NSCLC patients with rare EGFR mutations and combinations of mutationshttps://orcid.org/0000-0002-0698-7710СтуканьА. И.StukanA. I.

Стукань Анастасия Игоревна - к.м.н., доцент кафедры онкологии с курсом торакальной хирургии, КубГМУ; врач-онколог федеральной сети клиник «Евроонко».

350063, Краснодар, ул. Митрофана Седина, д. 4; 300050, Краснодар, ул. Северная, д. 315

Anastasiya I. Stukan - Cand. Sci. (Med.), Associate Professor of Department of Oncology with Thoracic Surgery Module, Kuban State Medical University; Oncologist, Euroonco Federal Network of Expert Oncology Clinics.

4, Mitrofan Sedin St., Krasnodar, 350063; 315, Severnaya St., Krasnodar, 300050

jolie86@bk.ruhttps://orcid.org/0000-0003-3206-8387ЕлкинА. В.ElkinA. V.

Елкин Антон Вадимович - врач-онколог, заведующий дневным стационаром федеральной сети клиник «Евроонко».

300050, Краснодар, ул. Северная, д. 315

Anton V. Elkin - Oncologist, Head of Day Patient Department, Euroonco Federal Network of Expert Oncology Clinics.

315, Severnaya St., Krasnodar, 300050

elkin@euroonco.ruhttps://orcid.org/0009-0007-0268-867XХореваД. В.KhorevaD. V.

Хорева Дарья Викторовна - аспирант кафедры онкологии с курсом торакальной хирургии, КубГМУ; врач-онколог федеральной сети клиник «Евроонко».

350063, Краснодар, ул. Митрофана Седина, д. 4; 300050, Краснодар, ул. Северная, д. 315

Daria V. Khoreva - Postgraduate Student of Department of Oncology with Thoracic Surgery Module, Kuban State Medical University; Oncologist, Euroonco Federal Network of Expert Oncology Clinics.

4, Mitrofan Sedin St., Krasnodar, 350063; 315, Severnaya St., Krasnodar, 300050

gorbachukd@mail.ruhttps://orcid.org/0000-0003-3169-9558БодняВ. Н.BodnyaV. N.

Бодня Вадим Николаевич - д.м.н., доцент кафедры онкологии с курсом торакальной хирургии, КубГМУ; врач-онколог, торакальный хирург, ККБ №1 им. проф. С.В. Очаповского.

350063, Краснодар, ул. Митрофана Седина, д. 4; 350086, Краснодар, ул. 1 Мая, д. 167

Vadim N. Bodnya - Dr. Sci. (Med.), Associate Professor of Department of Oncology with Thoracic Surgery Module, Kuban State Medical University; Oncologist, Thoracic Surgeon, Regional Clinical Hospital No. 1 named after Professor S.V. Ochapovsky.

4, Mitrofan Sedin St., Krasnodar, 350063; 167, 1st Maya St., Krasnodar, 350901

vadimbodnya@rambler.ruhttps://orcid.org/0000-0003-0572-1395ПорхановВ. А.PorkhanovV. A.

Порханов Владимир Алексеевич - академик РАН, чл.-корр. РАМН, д.м.н., профессор, заведующий кафедрой онкологии с курсом торакальной хирургии, КубГМУ; главный врач, ККБ №1 им. проф. С.В. Очаповского.

350063, Краснодар, ул. Митрофана Седина, д. 4; 350086, Краснодар, ул. 1 Мая, д. 167

Vladimir A. Porkhanov - Acad. RAS, Corr. Member RAS, Dr. Sci. (Med.), Professor, Head of Department of Oncology with Thoracic Surgery Module, Kuban State Medical University; Chief Medical Officer, Regional Clinical Hospital No. 1 named after Professor S.V. Ochapovsky.

4, Mitrofan Sedin St., Krasnodar, 350063; 167, 1st Maya St., Krasnodar, 350901

vladimirporhanov@mail.ruФедеральная сеть клиник «Евроонко»; Кубанский государственный медицинский университетРоссияEuroonco Federal Network of Expert Oncology Clinics; Kuban State Medical UniversityRussian FederationФедеральная сеть клиник «Евроонко»РоссияEuroonco Federal Network of Expert Oncology ClinicsRussian FederationКубанский государственный медицинский университет; Краевая клиническая больница №1 имени профессора С.В. ОчаповскогоРоссияKuban State Medical University; Regional Clinical Hospital No. 1 named after Professor S.V. OchapovskyRussian Federation2025010120260216066Copyright © Стукань А.И., Елкин А.В., Хорева Д.В., Бодня В.Н., Порханов В.А., 20262026Стукань А.И., Елкин А.В., Хорева Д.В., Бодня В.Н., Порханов В.А.Stukan A.I., Elkin A.V., Khoreva D.V., Bodnya V.N., Porkhanov V.A.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/9698

Эффективность таргетной терапии при редких мутациях гена рецептора эпидермального фактора роста (EGFR) при немелкоклеточном раке легких дискутабельна. Однако ввиду внедрения технологии NGS в клиническую практику все чаще выявляются больные немелкоклеточным раком легкого (НМРЛ) с редкими мутациями гена EGFR. Представленный клинический случай демонстрирует отсутствие мутаций гена EGFR на первичном этапе диагностики метастатической аденокарциномы легкого в ноябре 2024 г. С декабря 2024 г. было начато лечение в режиме пеметрексед + карбоплатин + бевацизумаб. В процессе лечения выполнено комплексное геномное профилирование по циркулирующей опухолевой ДНК (Foundation One Liquid CDx Roche). Выявлены редкая мутация экстрацеллюлярного домена E114K в гене EGFR и мутации CHEK2 – V335fs*14, PTPN11 – G503V, TP53 splice site 375G > T. C апреля 2025 г. назначен осимертиниб 80 мг/сут. После окончания 6-го курса полихимиотерапии и таргетной терапии (ПХТ + ТТ) в мае 2025 г. с учетом стабилизации заболевания, по данным позитронно-эмиссионной томографии, совмещенной с компьютерной томографией (ПЭТ-КТ) с 18F-ФДГ, пациент продолжает поддерживающую химиотаргетную терапию пеметрексед + осимертиниб со стабилизацией заболевания. Большинство исследований, которые привели к внедрению ингибиторов тирозинкиназ, исключали пациентов с редкими мутациями EGFR. Более того, в отношении многих мутаций до сих пор неясно, имеют ли они активирующий характер или являются просто случайными находками. Тем не менее имеющиеся отдельные клинические данные свидетельствуют о том, что ингибитор тирозинкиназ EGFR осимертиниб обладает клинической эффективностью при редких мутациях EGFR.

The efficacy of targeted therapy in rare epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer is debatable. However, due to introduction of NGS technology into clinical practice, patients with non-small cell lung cancer (NSCLC) harbouring rare EGFR mutations are being identified more often. We report here the case demonstrating the absence of EGFR mutations at the initial stage of diagnosis of metastatic lung adenocarcinoma in November 2024. The chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab was initiated in December 2024. During treatment, a comprehensive genomic profiling test (Foundation One Liquid CDx Roche) was performed to evaluate a patient’s blood for circulating tumour DNA (ctDNA). A rare EGFR E114K extracellular domain mutation and mutations in the cell cycle checkpoint kinase 2 (CHEK2) – V335fs*14, PTPN11 – G503V, and TP53 splice site 375G > T were identified. Osimertinib at a dose of 80 mg daily has been administered since April 2025. After the sixth course of polychemotherapy and targeted therapy (PCT+TT) in May 2025 and with due account for stabilization based on 18F-FDG PET-CT findings, the patient continued to receive the maintenance chemotargeted therapy with pemetrexed and osimertinib, showing disease stability. Most studies that led to the introduction of tyrosine kinase inhibitors excluded patients with rare EGFR mutations. Moreover, for many mutations, it is still unclear whether they are disease activating or merely incidental findings. Nevertheless, the available separate data suggest that osimertinib, EGFR tyrosine kinase inhibitor (EGFR-TKI), has clinical efficacy in rare EGFR mutations.

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