Systemic therapy of skin metastatic melanoma with BRAF gene mutation
https://doi.org/10.17709/2410-1893-2023-10-1-2
Abstract
Purpose of the study. To conduct a comparative analysis of the effectiveness of the use of mono‑mode immuno‑oncological and targeted drugs in the first line of therapy in patients with metastatic melanoma of the skin (SMM) in patients with BRAF mutation.
Patients and methods. To achieve this goal, a retrospective analysis of the treatment results was carried out in 61 patients diagnosed with metastatic melanoma of the skin and the presence of a mutation in the BRAF gene who were treated at the Yaroslavl regional oncology hospital. The patients were divided into two groups: the first group (n = 18) included patients who received mono‑mode immunotherapy in the first line of treatment; the second group (n = 43) included patients who underwent targeted first-line therapy.
Standard regimens of monotherapy with BRAF inhibitors (vemurafenib, dabrafenib) or combination therapy with BRAF and MEK inhibitors (dabrafenib + trametinib) were chosen as treatment. Immunotherapy was performed using the following drugs: pembrolizumab, nivolumab and prolgolimab. An intergroup comparative analysis of one‑year, three‑year and five‑year survival rates was carried out. Progression‑free survival rates and the frequency of objective responses were also studied.
Results. The median follow–up period in the first group was 14.2 months, in the second – 15.7 months. The indicators of one‑year, three-year and five‑year overall survival in patients receiving immunotherapy in the first line were 88.8 %, 55.5 % and 33.3 %, respectively. The same indicators in patients in the first‑line targeted therapy group were 90.7 %, 46.5 % and 23.2 %, respectively. The median overall survival in the first group was 39.1 months, in the second group it was 30.4 months. Progression–free survival in the group of patients with targeted therapy was 8.7 months, in the immunotherapy group – 9.8 months. In the first group, stabilization of the disease was observed in 77.8 % of patients, while a complete response was noted in 5.6 %, a partial response was not registered. In the second group of patients, stabilization was noted in 39.6 % of patients, partial response in 25.6 % of patients, complete response was absent.
Conclusion. The use of cancer immunotherapy drugs in the first line of treatment in patients with metastatic melanoma of the skin and the presence of BRAF mutation in the short term is not inferior in effectiveness to the use of targeted drugs, and in the medium and long term exceeds targeted drugs.
About the Authors
Yu. S. Shakh-ParonyantsRussian Federation
Yulia S. Shakh-Paronyants – MD, oncologist, Regional Clinical Oncology Hospital, Yaroslavl, Russian Federation
ORCID: https://orcid.org/0000-0002-5487-1691, SPIN-код: 5654-2788, AuthorID: 1100867
Competing Interests:
None
S. V. Cheporov
Russian Federation
Sergey Cheporov – Cand. Sci. (Med.), Chief of the Department of Antitumor Drug Therapy, Regional Clinical Oncology Hospital, Yaroslavl, Russian Federation; Associate Professor of the Department of Oncology with Hematology, State Medical University, Yaroslavl, Russian Federation
ORCID: https://orcid.org/0000-0003-2776-4994, SPIN-код: 6843-1441, AuthorID: 723405, Scopus Author ID: 25951379200
Competing Interests:
None
N. P. Shiryaev
Russian Federation
Nikolay P. Shiryaev – Assistant of the Department of Oncology with Hematology, Yaroslavl State Medical University, Yaroslavl, Russian Federation; Oncologist, Regional Clinical Oncology Hospital, Yaroslavl, Russian Federation
ORCID: https://orcid.org/0000-0002-9267-2730, SPIN-код: 5935-2465, AuthorID: 920882
Competing Interests:
None
A. V. Ukgarskiy
Russian Federation
Andrey Ukgarskiy – Cand. Sci. (Med.), Chief Physician Substitute for Strategic Development, Regional Clinical Oncology Hospital, Yaroslavl, Russian Federation
ORCID: https://orcid.org/0000-0001-5777-2261, SPIN: 7760-8952, AuthorID: 740058
Competing Interests:
None
P. V. Nesterov
Russian Federation
Pavel V. Nesterov – Cand. Sci. (Med.), Chief Physician of Regional Clinical Oncology Hospital, Yaroslavl, Russian Federation; Associate Professor of the Department of Urology with Nephrology, Yaroslavl State Medical University, Yaroslavl, Russian Federation
ORCID: https://orcid.org/0000-0002-7405-0305, SPIN-код: 6238-2354, AuthorID: 733962,
Competing Interests:
None
N. S. Korzina
Russian Federation
Nadezhda Korzina – Director Substitute of the Department of Health and Pharmacy of the Yaroslavl Region, Yaroslavl, Russian Federation
ORCID: https://orcid.org/0000-0002-2829-6830; SPIN-код: 5514-6142, AuthorID: 1168375
Competing Interests:
None
References
1. The state of oncological care to the population of Russia in 2021. Edited by A. D. Kaprin, V. V. Starinsky, A. O. Shakhzadova. Мoscow: P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, 2022, 239 p. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2022/05/sostoyanie-onkologicheskoj-pomoshhi-naseleniyu-rossii-v-2021-godu.pdf. Accessed: 05.02.2023.
2. World Health Organization. International Agency for Research of Cancer. Available at: https://www.iarc.who.int/. Accessed: 05.02.2023.
3. Ryan J. Sullivan. BRAF Targets in Melanoma. Biological Mechanism, Resistance, and Drug Discovery. New York, Humana; 2015; pp. 1–25.
4. Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, et al. Survival in BRAF V600‑mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707–714. https://doi.org/10.1056/nejmoa1112302
5. Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature. 2013 Feb 14;494(7436):251–255. https://doi.org/10.1038/nature11814
6. Robert C, Flaherty K, Nathan P, Hersey P, Garbe C, Milhem M, et al. Five‑year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K‑mutant advanced or metastatic melanoma. Eur J Cancer. 2019 Mar;109:61–69. https://doi.org/10.1016/j.ejca.2018.12.015
7. Long GV, Flaherty KT, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K‑mutant melanoma: long‑term survival and safety analysis of a phase 3 study. Ann Oncol. 2017 Jul 1;28(7):1631–1639. https://doi.org/10.1093/annonc/mdx176. Erratum in: Ann Oncol. 2019 Nov 1;30(11):1848
8. Michielin O, Akkooi А, Ascierto Р, Dummer R, Keilholz U. Cutaneous Melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow‑up. Annals of Oncology. 2019;30:1884–1901. https://doi.org/10.1093/annonc/mdz411
9. CHinese Acute Tissue‑Based Imaging Selection for Lysis In Stroke ‑Tenecteplase (CHABLIS‑T). Available at: https://clinicaltrials.gov/ct2/show/NCT02631447. Accessed: 05.02.2023.
10. Ascierto P, Mandala M, Ferrucci P, Rutkowski P, Guidoboni M, Arance Fernandezet AM, et al. First report of efficacy and safety from the phase II study SECOMBIT (Sequential COMBo Immuno and Targeted therapy study). Annals of Oncology. 2020;31(S4):1173–1174. https://doi.org/10.1016/j.annonc.2020.08.2275
11. Atkins MB, et al. DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG‑ACRIN EA6134. ASCO Plenary Series: November 2021 Session. J Clin Oncol. 2021;39 (suppl 36; abstr 356154).
12. Fernandez A, O’Day S, de la Cruz Merino L, Petrella T, Jamal R, Nyet L, et al. Lenvatinib (len) plus pembrolizumab (pembro) for advanced melanoma (MEL) progressed on a PD‑1 or PD‑L1 inhibitor: Initial results of LEAP‑004. Annals of Oncology. 2020;31(S4). https://doi.org/10.1016/j.annonc.2020.08.2274
13. Lipson EJ, Tawbi Hussein A‑H, Schadendorf D, Antonio PA, Matamala L, Gutiérrez EC, et al. Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first‑line advanced melanoma: Primary phase III results from RELATIVITY‑047 (CA224‑047). Journal of Clinical Oncology. 2021;39(15 Suppl):9504–9504. https://doi.org/10.1200/jco.2021.39.15_suppl.9503
14. Larkin J, Sarnaik A, Chesney JA, Khushalani NI, Kirkwood JM, Weber JS, et al. Lifileucel (LN‑144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti‑PD‑1 therapy. Journal of Clinical Oncology. 2021;39(15 Suppl):9505. https://doi.org/10.1200/jco.2021.39.15_suppl.9505
Supplementary files
Review
For citations:
Shakh-Paronyants Yu.S., Cheporov S.V., Shiryaev N.P., Ukgarskiy A.V., Nesterov P.V., Korzina N.S. Systemic therapy of skin metastatic melanoma with BRAF gene mutation. Research and Practical Medicine Journal. 2023;10(1):27-35. (In Russ.) https://doi.org/10.17709/2410-1893-2023-10-1-2