Encorafenib and binimetinib in the treatment of metastatic melanoma
DOI: 10.32364/2587-6821-2026-10-7-8
Encorafenib and binimetinib in the treatment of metastatic melanoma
I.V. Rykov1, A.R. Alekseeva1, E.K. Alieva2, V.I. Evdokimov3, T.N. Kochneva4, E.S. Kuzmina2, I.V. Myslevtsev4, V.S. Myagkova5, E.V. Lymar6, P.V. Koposov7, A.A. Kurmanaliev6, K.V. Orlova8, I.A. Sosnina3, A.V. Stupina9, V.A. Chubenko9,10, P.V. Eskina4, Yu.V. Puras11
1 MMC VT LLC, St. Petersburg, Russian Federation
2 S.S. Yudin City Clinical Hospital of the Moscow Healthcare Department, Moscow, Russian Federation
3 MMCC Kommunarka of the Moscow Healthcare Department, Moscow, Russian Federation
4 Botkin Hospital, Moscow, Russian Federation
5 Regional Clinical Oncology Center, Rostov-on-Don, Russian Federation
6 Regional Clinical Oncology Center No. 1, Krasnodar, Russian Federation
7 EMS Medical School, Private Continuing Professional Education Institution, Moscow, Russian Federation
8 N.A. Lopatkin Research Institute of Urology and Interventional Radiology — Branch of the National Medical Research Center of Radiology, Moscow, Russian Federation
9 N.P. Napalkov Saint Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care (Oncological), St. Petersburg, Russian Federation
10Saint Petersburg Medical and Social Institute, St. Petersburg, Russian Federation
11Pierre Fabre LLC, Moscow, Russian Federation
This paper reviews the Russian clinical experience with the BRAF/MEK inhibitor combination of encorafenib and binimetinib for the treatment of BRAF-mutant metastatic melanoma. It draws on findings from the international Phase III COLUMBUS trial as well as several observational studies conducted in real‑world clinical settings. The cumulative evidence demonstrates that this dual therapy not only extends progression‑free and overall survival but also maintains a manageable safety profile and preserves patients' quality of life. In addition, the authors present a series of clinical cases illustrating several practical applications of the encorafenib–binimetinib regimen: as a first‑line option in individuals with bulky disease, rapid progression, or extensive metastases (including intracranial involvement); as a switching strategy when other BRAF/MEK inhibitor combinations cause intolerable toxicity; and as a rechallenge approach after acquired resistance to prior targeted therapy. Collectively, these data reinforce the prominent role of encorafenib and binimetinib in contemporary treatment pathways for BRAF‑mutant melanoma and emphasize the ongoing need for further real‑world evidence to refine individualized patient care.
Keywords: metastatic melanoma, BRAF-mutation, targeted therapy, encorafenib, binimetinib.
For citation: Rykov I.V., Alekseeva A.R., Alieva E.K., Evdokimov V.I., Kochneva T.N., Kuzmina E.S., Myslevtsev I.V., Myagkova V.S., Lymar E.V., Koposov P.V., Kurmanaliev A.A., Orlova K.V., Sosnina I.A., Stupina A.V., Chubenko V.A., Eskina P.V., Puras Yu.V. Encorafenib and binimetinib in the treatment of metastatic melanoma. Russian Medical Inquiry. 2026;10(7):509–524 (in Russ.). DOI: 10.32364/2587-6821-2026-10-7-8
About the authors:
Ivan V. Rykov — C. Sc. (Med.), oncologist, Head of the Antitumor Drug Therapy Department, MMC VT LLC; Unit 1, build. 1, Klinika Beloostrov Territory, Yukkovskoye Rural Settlement, Vsevolozhsk Municipal District, Leningrad Region, 188632, Russian Federation; ORCID iD 0000-0002-8250-8144
Anastasia R. Alekseeva — oncologist, Antitumor Drug Therapy Department, MMC VT LLC; Unit 1, build. 1, Klinika Beloostrov Territory, Yukkovskoye Rural Settlement, Vsevolozhsk Municipal District, Leningrad Region, 188632, Russian Federation.
Enigyul K. Alieva — oncologist, Chemotherapy Department No. 3, S.S. Yudin City Clinical Hospital of the Moscow Healthcare Department; 4, Kolomensky pass., Moscow, 115446, Russian Federation; ORCID iD 0009-0009-0345-1847
Vladimir I. Evdokimov — Head of the Outpatient Oncology Care Center, oncologist, MMCC Kommunarka of the Moscow Healthcare Department; 8, build. 3, Sosensky Stan str., Kommunarka Village, Sosenskoye Settlement, Moscow, 108814, Russian Federation; ORCID iD 0000-0002-0591-7921
Tuyara N. Kochneva — oncologist, Outpatient Oncology Care Center, Botkin Hospital; 5, 2nd Botkinsky pass., Moscow, 125284, Russian Federation; ORCID iD 0009-0008-5412-6609
Evgenia S. Kuzmina — C. Sc. (Med.), oncologist, Head of Department, Oncology Center No. 1, S.S. Yudin City Clinical Hospital of the Moscow Healthcare Department; 4, Kolomensky pass., Moscow, 115446, Russian Federation; ORCID iD 0009-0007-2856-5176
Igor V. Myslevtsev — C. Sc. (Med.), oncologist, Head of Department, Outpatient Oncology Care Center, Botkin Hospital; 5, 2nd Botkinsky pass., Moscow, 125284, Russian Federation; ORCID iD 0000-0002-6821-1432
Valeria S. Myagkova — oncologist of the Day Hospital, Antitumor Drug Therapy Department No. 1, Regional Clinical Oncology Center; 9, Sokolov Ave., Rostov-on-Don, 344006, Russian Federation.
Elena V. Lymar — oncologist, Head of the Drug Supply Coordination Department, Regional Clinical Oncology Center No. 1; 146, Dimitrova str., Krasnodar, 350040, Russian Federation.
Pavel V. Koposov — Dr. Sc. (Med.), Professor, Deputy Director of the Institute of Oncology, Chief Medical Oncologist, Head of the Department of Medical and Clinical Oncology, EMS Medical School, Private Continuing Professional Education Institution; 35, Shchepkina str., Moscow, 129110, Russian Federation; ORCID iD 0000-0001-8789-9271
Artem A. Kurmanaliev — oncologist, Polyclinic Department, Regional Clinical Oncology Center No. 1; 146, Dimitrova str., Krasnodar, 350040, Russian Federation.
Kristina V. Orlova — Dr. Sc. (Med.), oncologist, Head of the Skin Tumor Department, N.A. Lopatkin Research Institute of Urology and Interventional Radiology — Branch of the National Medical Research Center of Radiology; 51 build. 1, 3rd Parkovaya str., Moscow, 105425, Russian Federation; ORCID iD 0000-0002-0442-5917
Irina A. Sosnina — oncologist, MMCC Kommunarka of the Moscow Healthcare Department; 8, build. 3, Sosensky Stan str., Kommunarka Village, Sosenskoye Settlement, Moscow, 108814, Russian Federation
Anastasia V. Stupina — oncologist, N.P. Napalkov Saint Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care (Oncological); 68, build. A, Leningradskaya str., Pesochny Settlement, St. Petersburg, 197758, Russian Federation; ORCID iD 0009-0003-2137-2188
Vyacheslav A. Chubenko — C. Sc. (Med.), Head of the Oncological Chemotherapy Department (Antitumor Drug Therapy) for Solid Tumors, N.P. Napalkov Saint Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care (Oncological); 68, build. A, Leningradskaya str., Pesochny Settlement, St. Petersburg, 197758, Russian Federation; Associate Professor of the Department of Oncology, Saint Petersburg Medical and Social Institute, Private Higher Education Institution; 72, build. A, Kondratyevsky Ave., St. Petersburg, 195271, Russian Federation; ORCID iD 0000-0001-6644-6687
Polina V. Eskina — oncologist, Day Hospital of Antitumor Drug Therapy, Botkin Hospital; 5, 2nd Botkinsky pass., Moscow, 125284, Russian Federation.
Yulia V. Puras — C. Sc. (Med.), Medical Department, Pierre Fabre LLC; Premise 2/1, 2, build. 1, Usacheva str., Khamovniki Municipal District, Moscow, 119048, Russian Federation; ORCID iD 0009-0007-3712-7821
Contact information: Ivan V. Rykov, e-mail: rykov.ivan@gmail.com
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
Conflict of interest: аuthor Yu.V. Puras is an employee of the Medical Department of Pierre Fabre LLC. This author's contribution was limited to the selection and provision of informational materials for the preparation of the manuscript text, as well as editing of the manuscript. No financial compensation was provided for these services.
Received 07.07.2026.
Revised 23.07.2026.
Accepted 30.07.2026.
2. Bray F., Laversanne M., Sung H. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263. DOI: 10.3322/caac.21834
3. Каприн, А.Д., Старинский В.В., Шахзадова А.О., Золотарев Н.Ю. Злокачественные новообразования в России в 2024 году (заболеваемость). М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радио-логии» Минздрава России; 2025. Kaprin A.D., Starinsky V.V., Shakhzadova A.O., Zolotarev N.Y. Malignant neoplasms in Russia in 2024 (morbidity). Moscow: P.A. Herzen Moscow Oncology Research Institute — branch of the National Medical Research Center of Radiology of the Ministry of Health of Russia; 2025 (in Russ.).
4. Castellani G., Buccarelli M., Arasi M.B. BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers. Cancers (Basel). 2023;15(16):4026. DOI: 10.3390/cancers15164026
5. Франк Г.А., Завалишина Л.Э., Кекеева Т.В. и др. Первое Всероссийское молекулярно-эпидемиологическое исследование меланомы: результаты анализа мутаций в гене BRAF. Архив патологии. 2014;3:65–73. Frank G.A., Zavalishina L.E., Kekeeva T.V. et al. The First All-Russian Molecular Epidemiological Study of Melanoma: Results of the Analysis of Mutations in the BRAF Gene. Archive of pathology. 2014;3:65–73 (in Russ.).
6. American Joint Committee on Cancer (AJCC). AJCC Cancer Staging Manual, 8th Ed. Chicago: Springer; 2017.
7. Ascierto P.A., Dummer R., Gogas H.J. et al. Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial. J Clin Oncol. 2023;41(29):4621–4631. DOI: 10.1200/JCO.22.02322
8. Flaherty K.T., Infante J.R., Daud A. et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694–1703. DOI: 10.1056/NEJMoa1210093
9. Dummer R., Ascierto P.A., Gogas H.J. et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF‑mutant melanoma (COLUMBUS): a multicentre, open‑label, randomized phase 3 trial. Lancet Oncol. 2018;19(5):603–615. DOI: 10.1016/S1470-2045(18)30142-6
10. Schadendorf D., Dummer R., Flaherty K.T. 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
11. Ascierto P.A., McArthur G.A., Dreno B. et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17(9):1248–1260. DOI: 10.1016/S1470-2045(16)30122-X
12. Heinzerling L., Eigentler T.K., Fluck M. et al. Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management. ESMO Open. 2019;4:e000491. DOI: 10.1136/esmoopen-2019-000491
13. Dandu H. The Role of Real-World Evidence in Oncology Drug Development: Current Capabilities and Future Potential. Int J Pharm Sci. 2025;3(9):2869–2879. DOI: 10.5281/zenodo.17193786
14. Soria A., Sanchez Mauriño P., Serrano Domingo J.J. et al. Real-life evidence of encorafenib plus binimetinib in patients with unresectable advanced or metastatic BRAFV600-mutant melanoma in Spain: the BECARE (GEM-2002) trial. Front Oncol. 2025;15:1466185. DOI: 10.3389/fonc.2025.1466185
15. Dummer R., Flaherty K.T., Robert C. et al. COLUMBUS 5‑Year Update: A Randomized, Open‑Label, Phase III Trial of Encorafenib Plus Binimetinib Versus Vemurafenib or Encorafenib in Patients With BRAF V600‑Mutant Melanoma. J Clin Oncol. 2022;40(36):4178–4188. DOI: 10.1200/JCO.21.02659
16. Richtig E., Loquai C., Forschner A. et al. Encorafenib plus binimetinib in patients with locally advanced, unresectable, or metastatic BRAF V600 -mutant melanoma: Updated data from the multicenter, multinational, prospective, non-interventional longitudinal study BERING MELANOMA. J Clin Oncol. 2022;40(16_suppl):9526–9526. DOI: 10.1200/JCO.2022.40.16_suppl.9526
17. In G.K., Chen K., Sajeev G. et al. 1117P Overall survival (OS) in patients with metastatic BRAF V600-mutant melanoma treated with encorafenib plus binimetinib (ENCO+BINI): Comparing real-world vs clinical trial data. Ann Oncol. 2023;34(2):S673. DOI: 10.1016/j.annonc.2023.09.2251
18. Yamazaki N., Sakata H., Iida O. et al. Post-marketing surveillance of encorafenib in combination with binimetinib in Japanese patients with BRAF-mutant melanoma. Int J Clin Oncol. 2025;30(4):814–823. DOI: 10.1007/s10147-025-02693-6
19. Czarnecka A.M., Błoński P., Cybulska-Stopa B. et al. Encorafenib with binimetinib efficacy in the first, second, and third line of treatment for patients with advanced melanoma harboring a BRAF mutation — real-world study Oncology in Clinical Practice. 2025. DOI: 10.5603/ocp.107991
20. Amaral T., Ottaviano M., Arance A. et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025;36(1):10–30. DOI: 10.1016/j.annonc.2024.11.006
21. Строяковский Д.Л., Абдулоева Н.Х., Демидов Л.В. и др. Меланома кожи. Клинические рекомендации RUSSCO, часть 1.2. Злокачественные опухоли. 2025;15(3s2):322–354. DOI: 10.18027/2224-5057-2025-15-3s2-1.2-12. Stroyakovsky D.L., Abduloeva N.Kh., Demidov L.V. et al. Melanoma of the skin. RUSSCO Clinical Guidelines, Part 1.2. Malignant tumors. 2025;15(3s2):322–354 (in Russ.). DOI: 10.18027/2224-5057-2025-15-3s2-1.2-12
22. Seth R., Agarwala S.S., Messersmith H. et al. Systemic Therapy for Melanoma: ASCO Guideline Update. J Clin Oncol. 2023;41(30):4794–4823. DOI: 10.1200/JCO.23.01136
23. Garbe C., Amaral T., Peris K. et al. European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization for Research and Treatment of Cancer (EORTC). European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment — Update 2024. Eur J Cancer. 2025;215:115153. DOI: 10.1016/j.ejca.2024.115153
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