medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2026-8-12-18medalphabet-5076Research ArticleСтатьиМеланома кожи. Современные перспективы в комплексном леченииSkin melanoma. Modern perspectives in complex treatmenthttps://orcid.org/0009-0009-7820-9801ПоныркоА. И.PonyrkoA. I.

Понырко Арина Игоревна, студентка

Москва

Ponyrko Arina I., student

Moscow

ГолубевП. В.GolubevP. V.

Голубев Павел Вячеславович, к. м. н., врач-онколог отделения противоопухолевой лекарственной терапии

г. Обнинск

Golubev Pavel V., PhD Med Sci, oncologist at Dept of Antitumor Drug Therapy

Obninsk

golubev194@gmail.comhttps://orcid.org/0009-0007-2856-5176КузьминаЕ. С.KuzminaE. S.

Кузьмина Евгения Сергеевна, к. м. н., зав. химиотерапевтическим отделением № 2 Онкологического центра № 1

Москва

Kuzmina Evgeniya S., PhD Med Sci, head of Chemotherapy Dept No. 2 of Oncology Center No. 1

Moscow

https://orcid.org/0009-0000-9658-3586КузьминВ. М.KuzminV. M.

Кузьмин Владислав Максимович, студент

Москва

Kuzmin Vladislav M., student

Moscow

https://orcid.org/0000-0002-0633-1738ГолубеваС. А.GolubevaS. A.

Голубева Софья Артемовна, врач-онколог отделения комбинированных методов лечения № 1

Москва

Golubeva Sofia A., oncologist at Dept of Combined Treatment Methods No. 1

Moscow

ФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова» Минздрава России (Сеченовский университет)РоссияI. M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationМедицинский радиологический научный центр им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский радиологический центр» Минздрава РоссииРоссияA. F. Tsyba Medical Radiology Research Center – branch of the National Medical Research Radiology CenterRussian FederationГБУЗ города Москвы «Городская клиническая больница имени С. С. Юдина Департамента здравоохранения города Москвы»РоссияS. S. Yudin City Clinical Hospital of the Moscow Department of HealthRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова» Минздрава России (Сеченовский университет)РоссияI. M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationМосковский научно-исследовательский онкологический институт им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский радиологический центр» Минздрава РоссииРоссияP. A. Herzen Moscow Cancer Research Institute – branch of the National Medical Research Radiology CenterRussian Federation20260406202608Диагностика и онкотерапия (1)1218Copyright © Понырко А.И., Голубев П.В., Кузьмина Е.С., Кузьмин В.М., Голубева С.А., 20262026Понырко А.И., Голубев П.В., Кузьмина Е.С., Кузьмин В.М., Голубева С.А.Ponyrko A.I., Golubev P.V., Kuzmina E.S., Kuzmin V.M., Golubeva S.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-alphabet.com/jour/article/view/5076

Меланома кожи – крайне агрессивное злокачественное новообразование, для которого характерны высокая смертность и частые рецидивы. За последние годы произошли революционные изменения в лечении данного заболевания. Внедрение в клиническую практику таргетной терапии и иммунотерапии значительно изменило традиционно неблагоприятный прогноз для многих пациентов, включая больных с нерезектабельной опухолью. Однако, несмотря на имеющийся прогресс, ответ на существующую терапию наблюдается не во всех случаях. Вкупе с растущей заболеваемостью это подчеркивает потребность в разработке новых терапевтических подходов и дальнейших исследованиях, направленных на оценку их эффективности и безопасности.

В данном обзоре обобщены долгосрочные результаты крупных исследований, уже оказавших влияние на клинические рекомендации, а также освещаются новые перспективные направления, которые могут изменить медицинскую практику в ближайшем будущем.

Melanoma of the skin is an extremely aggressive malignancy characterized by high mortality and frequent relapses. In recent years, revolutionary changes have occurred in the treatment of this disease. The introduction of targeted therapy and immunotherapy into clinical practice has significantly changed the traditionally unfavorable prognosis for many patients, including patients with unresectable tumors. However, despite the existing progress, the response to existing therapy is observed not in all cases. Together with the growing incidence, this emphasizes the need for the development of new therapeutic approaches and further studies aimed at assessing their efficacy and safety. This review summarizes the long-term results of large studies that have already influenced clinical guidelines and highlights new promising areas that may change medical practice in the near future.

меланомаиммуннотерапиятаргетная терапияпембролизумабниволумабипилимумабmelanomaimmunotherapytargeted therapypembrolizumabnivolumabipilimumabReferencesSun Y, Shen Y, Liu Q, et al. Global trends in melanoma burden: A comprehensive analysis from the Global Burden of Disease Study, 1990–2021. J Am Acad Dermatol. 2025; 92 (1): 100–107. DOI: 10.1016/j.jaad.2024.09.035 https://pubmed.ncbi.nlm.nih.gov/39343306/Sun Y, Shen Y, Liu Q, et al. Global trends in melanoma burden: A comprehensive analysis from the Global Burden of Disease Study, 1990–2021. J Am Acad Dermatol. 2025; 92 (1): 100–107. DOI: 10.1016/j.jaad.2024.09.035 https://pubmed.ncbi.nlm.nih.gov/39343306/Каприн А. Д. и др. Злокачественные новообразования в России в 2023 году (заболеваемость и смертность), 2024 https://oncology-association.ru/wp-content/uploads/2024/08/zis-2023-elektronnaya-versiya.pdfKaprin A. D. et al. Malignant neoplasms in Russia in 2023 (incidence and mortality), 2024. (In Russ.). https://oncology-association.ru/wp-content/uploads/2024/08/zis-2023-elektronnaya-versiya.pdfЭркенова Ф. Д., Пузин С. Н. Статистика меланомы в России и странах Европы // Медико-социальная экспертиза и реабилитация. 2020. Т. 23. № 1. C. 44–52. (In Russ.). DOI: 10.17816/MSER34259 https://cyberleninka.ru/article/n/statistika-melanomy-v-rossii-i-stranah-evropy/viewerErkenova F. D., Puzin S. N. Melanoma statistics in Russia and Europe // Medical and social examination and rehabilitation. 2020. Vol. 23. No. 1. P. 44–52. DOI: 10.17816/MSER34259 https://cyberleninka.ru/article/n/statistika-melanomy-v-rossii-i-stranah-evropy/viewerMeierjohann, S., Bertolotto, C. Messing with cancer therapy: how the melanoma phenotype predicts checkpoint inhibitor response. Sig Transduct Target Ther 9, 76, 2024. https://doi.org/10.1038/s41392–024–01785–5Meierjohann, S., Bertolotto, C. Messing with cancer therapy: how the melanoma phenotype predicts checkpoint inhibitor response. Sig Transduct Target Ther 9, 76, 2024. https://doi.org/10.1038/s41392–024–01785–5Andrea Boutros, Elena Croce, Marco Ferrari. The treatment of advanced melanoma: Current approaches and new challenges, Critical Reviews in Oncology/Hematology, Volume 196, 2024, https://doi.org/10.1016/j.critrevonc.2024.104276.Andrea Boutros, Elena Croce, Marco Ferrari. The treatment of advanced melanoma: Current approaches and new challenges, Critical Reviews in Oncology/Hematology, Volume 196, 2024, https://doi.org/10.1016/j.critrevonc.2024.104276.Голубев ПВ, Дешкина ТИ, Болотина ЛВ, Кузьмина ЕС, Голубева СА, Покатаев ИА, Галкин ВН. Клинический пример эффективности ингибитора антиPD‑1 (пролголимаб) при лечении метастатической меланомы. Медицинский Совет. 2024;(21):140–145. https://doi.org/10.21518/ms2024–515Golubev PV, Deshkina TI, Bolotina LV, Kuzmina ES, Golubeva SA, Pokataev IA, Galkin VN. Clinical example of the efficacy of an antiPD-1 inhibitor (prolgolimab) in the treatment of metastatic melanoma. Medical Council. 2024; (21):1 40–145. (In Russ.). https://doi.org/10.21518/ms2024–515F. Stephen Hodi et al. Long-term survival in advanced melanoma for patients treated with nivolumab plus ipilimumab in CheckMate 067.. JCO 40, 9522–9522, 2022. DOI: 10.1200/JCO.2022.40.16_suppl.9522 https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9522F. Stephen Hodi et al. Long-term survival in advanced melanoma for patients treated with nivolumab plus ipilimumab in CheckMate 067.. JCO 40, 9522–9522, 2022.DOI: 10.1200/JCO.2022.40.16_suppl.9522 https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9522Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025; 392 (1): 11–22. DOI: 10.1056/NEJMoa2407417 https://www.nejm.org/doi/full/10.1056/NEJMoa2407417Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025; 392 (1): 11–22. DOI: 10.1056/NEJMoa2407417 https://www.nejm.org/doi/full/10.1056/NEJMoa2407417Paolo Antonio Ascierto et al. Efficacy and safety of triplet nivolumab, relatlimab, and ipilimumab (NIVO + RELA + IPI) in advanced melanoma: Results from RELATIVITY‑048. JCO 42, 9504–9504, 2024. DOI: 10.1200/JCO.2024.42.16_suppl.9504 https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9504Paolo Antonio Ascierto et al. Efficacy and safety of triplet nivolumab, relatlimab, and ipilimumab (NIVO + RELA + IPI) in advanced melanoma: Results from RELATIVITY‑048. JCO 42, 9504–9504, 2024. DOI: 10.1200/JCO.2024.42.16_suppl.9504 https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9504Schadendorf, Dirk et al. Prognostic value of patient-reported outcomes in advanced or metastatic melanoma patients treated with immunotherapy: Findings from the CheckMate‑067 study. European Journal of Cancer, Volume 213, 115099, 2024 DOI: 10.1016/j.ejca.2024.115099 https://www.ejcancer.com/article/S0959–8049(24)01706–4/fulltextSchadendorf, Dirk et al. Prognostic value of patient-reported outcomes in advanced or metastatic melanoma patients treated with immunotherapy: Findings from the CheckMate‑067 study. European Journal of Cancer, Volume 213, 115099, 2024 DOI: 10.1016/j.ejca.2024.115099 https://www.ejcancer.com/article/S0959–8049(24)01706–4/fulltextVosoughi, E., Lee, J.M., Miller, J.R. et al. Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies. BMC Cancer 18, 490, 2018. https://doi.org/10.1186/s12885–018–4374-x https://bmccancer.biomedcentral.com/articles/10.1186/s12885–018–4374-xVosoughi, E., Lee, J.M., Miller, J.R. et al. Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies. BMC Cancer 18, 490, 2018. https://doi.org/10.1186/s12885–018–4374-x https://bmccancer.biomedcentral.com/articles/10.1186/s12885–018–4374-xLong GV, Atkinson V, Lo SN, et al. Ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases (ABC): 7-year follow-up of a multicentre, open-label, randomised, phase 2 study. Lancet Oncol. 2025; 26 (3): 320–330. DOI: 10.1016/S1470–2045(24)00735–6 https://pubmed.ncbi.nlm.nih.gov/39978375/Long GV, Atkinson V, Lo SN, et al. Ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases (ABC): 7-year follow-up of a multicentre, open-label, randomised, phase 2 study. Lancet Oncol. 2025; 26 (3): 320–330. DOI: 10.1016/S1470–2045(24)00735–6 https://pubmed.ncbi.nlm.nih.gov/39978375/Ascierto PA, Mandalà M, Ferrucci PF, et al. Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma. NEJM Evid. 2024;3(10): EVIDoa2400087. DOI: 10.1056/EVIDoa2400087 https://evidence.nejm.org/doi/10.1056/EVIDoa2400087Ascierto PA, Mandalà M, Ferrucci PF, et al. Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma. NEJM Evid. 2024;3(10): EVIDoa2400087. DOI: 10.1056/EVIDoa2400087 https://evidence.nejm.org/doi/10.1056/EVIDoa2400087Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023; 41 (2): 186–197. DOI: 10.1200/JCO.22.01763 https://pubmed.ncbi.nlm.nih.gov/36166727/Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023; 41 (2): 186–197. DOI: 10.1200/JCO.22.01763 https://pubmed.ncbi.nlm.nih.gov/36166727/Schadendorf D, Dummer R, Flaherty KT, et al. COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600E/K-mutant melanoma. Eur J Cancer. 2024; 204: 114073. DOI: 10.1016/j.ejca.2024.114073 https://www.ejcancer.com/article/S0959–8049(24)00729–9/fulltextSchadendorf D, Dummer R, Flaherty KT, et al. COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600E/K-mutant melanoma. Eur J Cancer. 2024; 204: 114073. DOI: 10.1016/j.ejca.2024.114073 https://www.ejcancer.com/article/S0959–8049(24)00729–9/fulltextGutzmer R, Stroyakovskiy D, Gogas H, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2020 Aug 15; 396 (10249): 466. DOI: 10.1016/S0140–6736(20)31721–9.]. Lancet. 2020;395(10240):1835–1844. DOI: 10.1016/S0140–6736(20)30934-X https://pubmed.ncbi.nlm.nih.gov/32534646/Gutzmer R, Stroyakovskiy D, Gogas H, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2020 Aug 15; 396 (10249): 466. DOI: 10.1016/S0140–6736(20)31721–9.]. Lancet. 2020;395(10240):1835–1844. DOI: 10.1016/S0140–6736(20)30934-X https://pubmed.ncbi.nlm.nih.gov/32534646/Dummer R, Long GV, Robert C, et al. Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma. J Clin Oncol. 2022; 40 (13): 1428–1438. DOI: 10.1200/JCO.21.01601 https://pubmed.ncbi.nlm.nih.gov/35030011/Dummer R, Long GV, Robert C, et al. Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma. J Clin Oncol. 2022; 40 (13): 1428–1438. DOI: 10.1200/JCO.21.01601 https://pubmed.ncbi.nlm.nih.gov/35030011/18 – Ascierto PA, Ferrucci PF, Fisher R, et al. Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. Nat Med. 2019; 25 (6): 941–946. DOI: 10.1038/s41591–019–0448–9 https://pubmed.ncbi.nlm.nih.gov/31171878/18 – Ascierto PA, Ferrucci PF, Fisher R, et al. Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. Nat Med. 2019; 25 (6): 941–946. DOI: 10.1038/s41591–019–0448–9 https://pubmed.ncbi.nlm.nih.gov/31171878/Dudnichenko O, Penkov K, McKean M, et al. First-line encorafenib plus binimetinib and pembrolizumab for advanced BRAF V600-mutant melanoma: Safety lead-in results from the randomized phase III STARBOARD study. Eur J Cancer. 2024; 213: 115070. DOI: 10.1016/j.ejca.2024.115070 https://www.ejcancer.com/article/S0959–8049(24)01201–2/fulltext#supplementary-materialDudnichenko O, Penkov K, McKean M, et al. First-line encorafenib plus binimetinib and pembrolizumab for advanced BRAF V600-mutant melanoma: Safety lead-in results from the randomized phase III STARBOARD study. Eur J Cancer. 2024; 213: 115070. DOI: 10.1016/j.ejca.2024.115070 https://www.ejcancer.com/article/S0959–8049(24)01201–2/fulltext#supplementary-materialVersluis JM, Menzies AM, Sikorska K, et al. Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials. Ann Oncol. 2023; 34 (4): 420–430. DOI: 10.1016/j.annonc.2023.01.004 https://www.annalsofoncology.org/article/S0923–7534(23)00035–2/fulltextVersluis JM, Menzies AM, Sikorska K, et al. Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials. Ann Oncol. 2023; 34 (4): 420–430. DOI: 10.1016/j.annonc.2023.01.004 https://www.annalsofoncology.org/article/S0923–7534(23)00035–2/fulltextBlank CU, Lucas MW, Scolyer RA, et al. Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma. N Engl J Med. 2024; 391 (18): 1696–1708. DOI: 10.1056/NEJMoa2402604 https://www.nejm.org/doi/full/10.1056/NEJMoa2402604Blank CU, Lucas MW, Scolyer RA, et al. Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma. N Engl J Med. 2024; 391 (18): 1696–1708. DOI: 10.1056/NEJMoa2402604 https://www.nejm.org/doi/full/10.1056/NEJMoa2402604Long, G.V., Carlino, M.S., Au-Yeung, G. et al. Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAFV600-mutant resectable melanoma: the randomized phase 2 NeoTrio trial. Nat Med 30, 2540–2548 2024. https://doi.org/10.1038/s41591–024–03077–5 https://www.nature.com/articles/s41591–024–03077–5#Sec2Long, G.V., Carlino, M.S., Au-Yeung, G. et al. Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAFV600-mutant resectable melanoma: the randomized phase 2 NeoTrio trial. Nat Med 30, 2540–2548 2024. https://doi.org/10.1038/s41591–024–03077–5 https://www.nature.com/articles/s41591–024–03077–5#Sec2Luke JJ, Rutkowski P, Queirolo P, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE‑716): a randomised, double-blind, phase 3 trial. Lancet. 2022; 399 (10336): 1718–1729. DOI:10.1016/S0140–6736(22)00562–1 https://pubmed.ncbi.nlm.nih.gov/35367007/Luke JJ, Rutkowski P, Queirolo P, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE‑716): a randomised, double-blind, phase 3 trial. Lancet. 2022; 399 (10336): 1718–1729. DOI:10.1016/S0140–6736(22)00562–1 https://pubmed.ncbi.nlm.nih.gov/35367007/Luke JJ, Ascierto PA, Khattak MA, et al. Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE‑716 Study. J Clin Oncol. 2024; 42 (14): 1619–1624. DOI: 10.1200/JCO.23.02355 https://pubmed.ncbi.nlm.nih.gov/38452313/Luke JJ, Ascierto PA, Khattak MA, et al. Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE‑716 Study. J Clin Oncol. 2024; 42 (14): 1619–1624. DOI: 10.1200/JCO.23.02355 https://pubmed.ncbi.nlm.nih.gov/38452313/

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