Changes in clinical guidelines of 2023 and 2025 on treatment of cutaneous and mucosal melanoma

Cover Page

Cite item

Full Text

Abstract

The article presents a comparative analysis of Russian clinical recommendations on treatment of melanoma of the skin and mucous membranes during a period of 2020 and 2023, as well as foreign recommendations of N CCN (National Comprehensive Cancer Network) and ESMO (European Society for Medical Oncology) of 2025. The main debatable issues related to changes on melanoma therapy in 2025 are presented for discussion. The topic of modifying the treatment of patients with melanoma with metastases in the brain is highlighted. New treatment options for patients with metastatic and unresectable (stage IIIC–D) melanoma are discussed, as well as the neoadjuvant and adjuvant therapy options for stage II–III cutaneous melanoma. Various treatment options for patients with local stage melanoma are considered. Among other, the recommendations of 2025 are supplemented with treatment options for melanoma in children.
Aim. To highlight changes in clinical guidelines for treatment of melanoma of the skin and mucous membranes for use in daily clinical practice.

About the authors

I. V. Samoylenko

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-7150-5071

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

Ya. V. Belenkaya

2I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: yana-belenkaya@bk.ru
ORCID iD: 0000-0003-2163-1752

24 Kashirskoe Shosse, Moscow 115522

Build. 2, 8 Trubetskaya St., Moscow 119048

Russian Federation

M. E. Abramov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-4754-2352

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

M. D. Aliev

P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-2706-4138

3 2nd Botkinskiy Proezd, Moscow 125284

Russian Federation

S. M. Banov

N.N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-6510-7883

16 4th Tverskaya-Yamskaya St., Moscow 125047

Russian Federation

T. S. Belysheva

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-5911-553X

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

G. I. Gafton

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-3172-2201

68 Leningradskaya St., Pesochnyy, Saint Petersburg 197758

Russian Federation

A. V. Golanov

N.N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-0976-4547

16 4th Tverskaya-Yamskaya St., Moscow 125047

Russian Federation

L. V. Demidov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-8562-6082

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

N. V. Zhukova

Saint Petersburg City Clinical Oncology Dispensary

Email: fake@neicon.ru
ORCID iD: 0000-0002-0619-2205

56 Prospekt Veteranov, Saint Petersburg 198255

Russian Federation

A. R. Zaretskiy

Research Institute of Translational Medicine, N. I. Pirogov Russian National Research Medical University; M.M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry

Email: fake@neicon.ru
ORCID iD: 0000-0002-7778-6617

Build. 1, 1 Ostrovityanova St., Moscow 117513

16 / 10 Miklukho-Maklaya St., Moscow 117997

Russian Federation

V. V. Mordovtseva

Russian Biotechnology University (Rosbiotekh)

Email: fake@neicon.ru
ORCID iD: 0000-0002-6396-2720

11 Volokolamskoye Shosse, Moscow 125080

Russian Federation

A. V. Novik

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-2430-4709

68 Leningradskaya St., Pesochnyy, Saint Petersburg 197758

Russian Federation

K. V. Orlova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-0442-5917

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

E. K. Saribekyan

P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-0307-8252

3 2nd Botkinskiy Proezd, Moscow 125284

Russian Federation

O. P. Trofimova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-7204-370X

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

A. A. Fedenko

P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-4927-5585

3 2nd Botkinskiy Proezd, Moscow 125284

Russian Federation

T. K. Kharatishvili

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-8135-4841

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

G. Yu. Kharkevich

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-5487-2299

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

A. N. Yurchenkov

Moscow City Oncology Hospital No. 62, Moscow Healthcare Department

Email: fake@neicon.ru
ORCID iD: 0000-0003-1973-1092

27 Istra, Moscow Region 143515

Russian Federation

References

  1. Luke J.J., 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):1718–29. doi: 10.1016/S0140-6736(22)00562-1
  2. Kirkwood J.M., del Vecchio M., Weber J. et al. Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med 2023;29(11):2835–43. doi: 10.1038/s41591-023-02583-2
  3. Blank C.U., Rozeman E.A., Fanchi L.F. et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med 2018;24(11):1655–61. doi: 10.1038/s41591-018-0198-0
  4. Rozeman E.A., Menzies A.M., van Akkooi A.C.J. et al. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial. Lancet Oncol 2019;20(7):948–60. doi: 10.1016/S1470-2045(19)30151-2
  5. Blank C.U., Lucas M.W., Scolyer R.A. et al. Neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in macroscopic, resectable stage III melanoma: the phase 3 NADINA trial. J Clin Oncol 2024;42(suppl 17):LBA2. doi: 10.1200/JCO.2024.42.17_suppl.LBA2
  6. Blank C.U., Reijers I.L.M., Saw R.P.M. et al. Survival data of PRADO: A phase 2 study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma. J Clin Oncol 2022;40(suppl_16):9501. doi: 10.1200/JCO.2022.40.16_suppl.9501
  7. 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):4178–88. doi: 10.1200/JCO.21.02659
  8. 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, openlabel, randomised phase 3 trial. Lancet Oncol 2018;19(5):603–15. doi: 10.1016/S1470-2045(18)30142-6
  9. Gogas H., Dummer R., Ascierto P.A. et al. Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: results from a multicentre, open-label, randomised, phase III study (COLUMBUS). Eur J Cancer 2021;152:116–28. doi: 10.1016/j.ejca.2021.04.028
  10. Lebbe C., Meyer N., Mortier L. et al. Evaluation of two dosing regimens for nivolumab in combination with ipilimumab in patients with advanced melanoma: results from the phase IIIb/IV CheckMate 511 Trial. J Clin Oncol 2019;37(11):867–75. doi: 10.1200/JCO.18.01998
  11. Olson D.J., Eroglu Z., Brockstein B. et al. Pembrolizumab plus ipilimumab following anti-PD-1/L1 failure in melanoma. J Clin Oncol 2021;39(24):2647–55. doi: 10.1200/JCO.21.00079
  12. Samoylenko I.V., Demidov L.V., Moiseenko V.M. et al. Efficacy and safety of nurulimab + prolgolimab with continued prolgolimab therapy compared to prolgolimab alone as first-line therapy in patients with unresectable or metastatic melanoma: final results of the phase II OBERTON clinical study. Sovremennaya onkologiya = Journal of Modern Oncology 2023;25(3):313–24. (In Russ.). doi: 10.26442/18151434.2023.3.202463
  13. Demidov L., Samoylenko I., Kharkevich G. et al. Proved clinical benefit of low-dose anti-CTLA4 + anti-PD-1 immunotherapy versus mono anti-PD-1 therapy in patients unresectable or metastatic melanoma: phase III OCTAVA trial (abstract). Cancer Res 2025;85(8_Suppl_1):653. doi: 10.1158/1538-7445.AM2025-653
  14. Samoylenko I.V., Kolontareva Yu.M., Kogay E.V. et al. Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in the Russian Federation: results of the A1 cohort of the ISABELLA study. Front Oncol 2024;14:1395378. doi: 10.3389/fonc.2024.1395378
  15. Gutzmer R., Stroyakovskiy D., Gogaset H. et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF(V600) mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020;395(10240):1835–44. doi: 10.1016/S0140-6736(20)30934-X
  16. Ferrucci P.F., Di Giacomo A.M., Del Vecchio M. et al. KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma. J Immunother Cancer 2020;8(2):e001806. doi: 10.1136/jitc-2020-001806
  17. Arance A., de la Cruz-Merino L., Petrella T.M. et al. Phase II LEAP-004 study of lenvatinib plus pembrolizumab for melanoma with confirmed progression on a programmed cell death protein-1 or programmed death ligand 1 inhibitor given as monotherapy or in combination. J Clin Oncol 2023;41(1):75–85. doi: 10.1200/JCO.22.00221
  18. Robert C., Ribas A., Schachter J. et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol 2019;20(9):1239–51. doi: 10.1016/S1470-2045(19)30388-2
  19. Schadendorf D., Hassel J.C., Fluck M. et al. Adjuvant immunotherapy with nivolumab (NIVO) alone or in combination with ipilimumab (IPI) versus placebo in stage IV melanoma patients with no evidence of disease (NED): a randomized, double-blind phase II trial (IMMUNED). Ann Oncol 2019;30:v903–v904. doi: 10.1093/annonc/mdz394.064
  20. Andtbacka R.H., Kaufman H.L., Collichio F. et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 2015;33(25):2780–8. doi: 10.1200/JCO.2014.58.3377
  21. Kunte C., Letulé V., Gehl J. et al. Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT. Br J Dermatol 2017;176(6):1475–85. doi: 10.1111/bjd.15340
  22. Tawbi H.A., Hodi F.S., Lipson E.J. et al. Nivolumab (NIVO) plus relatlimab (RELA) versus NIVO in previously untreated metastatic or unresectable melanoma (RELATIVITY-047): overall survival (OS) and melanoma-specific survival (MSS) outcomes at 3 years. J Clin Oncol 2024;42(suppl_16):9524. doi: 10.1200/JCO.2024.42.16_suppl.9524
  23. Ascierto P.A., Dummer R., Gaudy-Marqueste C. et al. Efficacy and safety of triplet nivolumab, relatlimab, and ipilimumab (NIVO + RELA + IPI) in advanced melanoma: results from RELATIVITY-048. J Clin Oncol 2024;42(suppl_16):9504. doi: 10.1200/JCO.2024.42.16_suppl.9504
  24. Rohaan M.W., Borch T.H., van den Berg J.H. et al. Tumorinfiltrating lymphocyte therapy or ipilimumab in advanced melanoma. N Engl J Med 2022;387(23):2113–25. doi: 10.1056/NEJMoa2210233
  25. Schoenfeld A.J., Lee S.M., de Spéville B.D. et al. Lifileucel, an autologous tumor-infiltrating lymphocyte monotherapy, in patients with advanced non-small cell lung cancer resistant to immune checkpoint inhibitors. Cancer Discov 2024;14(8): 1389–402. doi: 10.1158/2159-8290.CD-23-1334
  26. Robert C., Dutriaux C., Oppong F.B. et al. Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced BRAF-V600E/K-mutated melanoma: The primary analysis of an EORTC randomized phase II study (EBIN). J Clin Oncol 2024;42(suppl_17):LBA9503. doi: 10.1200/JCO.2024.42.17_suppl.LBA9503
  27. Vogelbaum M.A., Brown P.D., Messersmith H. et al. Treatment for brain metastases: ASCO-SNO-ASTRO Guideline. J Clin Oncol 2022;40(5):492–516. doi: 10.1200/JCO.21.02314
  28. Hasanov M., Martin B., Hasanov E. et al. The 31-GEP to identify patients with localized cutaneous melanoma at the highest risk of metastasis to the central nervous system. J Clin Oncol 2024; 42(suppl_16):9530. doi: 10.1200/JCO.2024.42.16_suppl.9530
  29. Le Rhun E., Guckenberger M., Smits M. et al. EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumors. Ann Oncol 2021;32(11):1332–47. doi: 10.1016/j.annonc.2021.07.016
  30. Sperduto P.W., Mesko S., Li J. et al. Survival in patients with brain metastases: summary report on the updated diagnosis-specific graded prognostic assessment and definition of the eligibility quotient. J Clin Oncol 2020;38(32):3773–84. doi: 10.1200/JCO.20.01255
  31. Amaral T., Chatziioannou E., Nuebling A. et al. Identification of patients at high risk for relapse using the Merlin Assay (CP-GEP) in an independent cohort of 451 patients (pts) with stage I/II melanoma who did not undergo sentinel lymph node biopsy. J Clin Oncol 2024;42(suppl_16):9574. doi: 10.1200/JCO.2024.42.16_suppl.9574
  32. Khan M., Zhao Z., Arooj S., Liao G. Bevacizumab for radiation necrosis following radiotherapy of brain metastatic disease: a systematic review & meta-analysis. BMC Cancer 2021;21(1):167. doi: 10.1186/s12885-021-07889-3
  33. Liew D.N., Kano H., Kondziolka D. et al. Outcome predictors of Gamma Knife surgery for melanoma brain metastases. Clinical article. J Neurosurg 2011;114(3):769–79. doi: 10.3171/2010.5.JNS1014
  34. Geoerger B., Kang H.J., Yalon-Oren M. et al. Pembrolizumab in pediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumor or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1–2 trial. Lancet Oncol 2020;21(1):121–33. doi: 10.1016/S1470-2045(19)30671-0
  35. Geoerger B., Bergeron C., Gore L. et al. Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma. Eur J Cancer 2017;86:358–63. doi: 10.1016/j.ejca.2017.09.032
  36. Merchant M.S., Wright M., Baird K. et al. Phase I clinical trial of ipilimumab in pediatric patients with advanced solid tumors. Clin Cancer Res 2016;22(6):1364–70. doi: 10.1158/1078-0432.CCR-15-0491
  37. Weyand A.C., Mody R.J., Rabah R.M., Opipari V.P. PD-1 inhibition in congenital pigment synthesizing metastatic melanoma. Pediatr Blood Cancer 2018;65(1). doi: 10.1002/pbc.26702
  38. Chisholm J.C., Suvada J., Dunkel I.J. et al. BRIM-P: a phase I, open-label, multicenter, dose-escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF mutationpositive melanoma. Pediatr Blood Cancer 2018;65(5):e26947. doi: 10.1002/pbc.26947
  39. Bay S.B., Kebudi R., Zulfikar B. Cutaneous adverse event associated with vemurafenib in a 3-year-old pediatric patient with BRAF mutation-positive metastatic melanoma and factor X deficiency. Melanoma Res 2019;29(1):99–101. doi: 10.1097/CMR.0000000000000537
  40. Bay S.B., Gorgun O., Kebudi R. Children with malignant melanoma: a single center experience from Turkey. Turk Pediatri Ars 2020;55(1):39–45. doi: 10.14744/TurkPediatriArs.2019.90022
  41. Boddie A.W. Jr, Cangir A. Adjuvant and neoadjuvant chemotherapy with dacarbazine in high-risk childhood melanoma. Cancer 1987;60(8):1720–3. doi: 10.1002/1097-0142(19871015)60:8<1720::aidcncr2820600805>3.0.co;2-h
  42. Wada H., Nemoto K., Ogawa Y. et al. A multi-institutional retrospective analysis of external radiotherapy for mucosal melanoma of the head and neck in Northern Japan. Int J Radiat Oncol Biol Phys 2004;59(2):495–500. doi: 10.1016/j.ijrobp.2003.11.013
  43. Samstein R.M., Carvajal R.D., Postow M.A. et al. Localized sinonasal mucosal melanoma: outcomes and associations with stage, radiotherapy, and positron emission tomography response. Head Neck 2016;38(9):1310–7. doi: 10.1002/hed.24435
  44. Saigal K., Weed D.T., Reis I.M. et al. Mucosal melanomas of the head and neck: the role of postoperative radiation therapy. ISRN Oncol 2012;2012:785131. doi: 10.5402/2012/785131
  45. Plavc G., But-Hadzic J., Anicin A. et al. Mucosal melanoma of the head and neck: a population-based study from Slovenia, 1985–2013. Radiat Oncol 2016;11(1):137. doi: 10.1186/s13014-016-0712-9
  46. Krengli M., Masini L., Kaanders J.H. et al. Radiotherapy in the treatment of mucosal melanoma of the upper aerodigestive tract: analysis of 74 cases. A Rare Cancer Network study. Int J Radiat Oncol Biol Phys 2006;65(3):751–9. doi: 10.1016/j.ijrobp.2006.01.016

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c)


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ЭЛ № ФС 77 - 85909 от  25.08.2023.