The Current Successes (and Failures) in the Treatment of Cutaneous Metastatic Melanoma
Main Article Content
Abstract
The contemporaneous treatment of cutaneous metastatic melanoma (CMM) has been revolutionized in a process started decades ago with the better understanding of cancer genetics, cancer biology and the functioning mechanisms of the immune system, which were more recently translated from basic and clinical research into efficacious and effective new drugs. At the turn of the 21st century, patients with CMM had very few treatment options and their survival was measured in few months. Traditional chemotherapy or cytotoxic drugs had very limited non curative potential, with OS in the ranging from 6 to 12 months, at best.
Currently, the use of immune check point inhibitors (ICIs) and drugs directed at blocking mutated BRAF gene proteins as well as MEK inhibitors have transformed the landscape of CMM treatment, with immense positive impact on hard surrogates such as overall survival (OS) and disease-free survival (DFS) and on the quality of life (QoL) of such patients.
Our objective here is to review the last ten years of data regarding this evolution, as well as acknowledging its pitfalls and limitations, while trying to look forward in the search for biomarkers that could better tail treatment choices while preventing unnecessary toxicities.
Article Details
How to Cite
JC, Coelho et al.
The Current Successes (and Failures) in the Treatment of Cutaneous Metastatic Melanoma.
Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4751>. Date accessed: 03 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i11.4751.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Kim KB, Sosman JA, Fruehauf JP, et al. BEAM: A Randomized Phase II Study Evaluating the Activity of Bevacizumab in Combination with Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Melanoma. J Clin Oncol. 2012;30(1):34-41. doi:10.1200/JCO.2011.34.6270
3. Rosenberg SA, Yang JC, White DE, Steinberg SM. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg. 1998;228(3):307-319.
4. Atkins MB, Lotze MT, Dutcher JP, et al. High-Dose Recombinant Interleukin 2 Therapy for Patients With Metastatic Melanoma: Analysis of 270 Patients Treated Between 1985 and 1993. J Clin Oncol. 1999;17(7):2105-2105. doi:10.1200/JCO.1999.17.7.2105
5. Atkins MB, Hsu J, Lee S, et al. Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2008;26(35):5748-5754. doi:10.1200/JCO.2008.17.5448
6. Atkins MB, Buzaid AC, Houghton AN Jr. Chemotherapy and biochemotherapy. In: Cutaneous Melanoma. Balch C, Houghton A, Sober A, Soong S, Eds. 4th edition. Quality Medical Publishing; 2003:589.
7. Ives NJ, Stowe RL, Lorigan P, Wheatley K. Chemotherapy Compared With Biochemotherapy for the Treatment of Metastatic Melanoma: A Meta-Analysis of 18 Trials Involving 2,621 Patients. J Clin Oncol. 2007;25(34):5426-5434. doi:10.1200/JCO.2007.12.0253
8. García-Gutiérrez V, Hernández-Boluda JC. Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety. Front Oncol. 2019;9. Accessed October 1, 2023. https://www.frontiersin.org/articles/10.3389/fonc.2019.00603
9. Smyth MJ, Teng MW. 2018 Nobel Prize in physiology or medicine. Clin Transl Immunol. 2018;7(10):e1041. doi:10.1002/cti2.1041
10. Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 2011;144(5):646-674. doi:10.1016/j.cell.2011.02.013
11. Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31-46. doi:10.1158/2159-8290.CD-21-1059
12. Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol. 2016;39(1):98. doi:10.1097/COC.0000000000000239
13. Lipson EJ, Drake CG. Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(22):6958-6962. doi:10.1158/1078-0432.CCR-11-1595
14. Ralli M, Botticelli A, Visconti IC, et al. Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions. J Immunol Res. 2020;2020:e9235638. doi:10.1155/2020/9235638
15. Long L, Zhang X, Chen F, et al. The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes Cancer. 2018;9(5-6):176-189. doi:10.18632/genesandcancer.180
16. Passarelli A, Mannavola F, Stucci LS, Tucci M, Silvestris F. Immune system and melanoma biology: a balance between immunosurveillance and immune escape. Oncotarget. 2017;8(62):106132-106142. doi:10.18632/oncotarget.22190
17. Hodi FS, O’Day SJ, McDermott DF, et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med. 2010;363(8):711-723. doi:10.1056/NEJMoa1003466
18. Robert C, Long GV, Brady B, et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. N Engl J Med. 2015;372(4):320-330. doi:10.1056/NEJMoa1412082
19. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521-2532. doi:10.1056/NEJMoa1503093
20. Coelho JC, Rebelatto TF, Pereira RR, Liedke PER, Zanon AB, Azevedo SJ. Atezolizumab Monotherapy as First-line Treatment in Patients with Advanced BRAFV600 Wild-type Melanoma. J Clin Haematol. 2021;Volume 2(Issue 3):95-97. doi:10.33696/haematology.2.034
21. de Azevedo SJ, de Melo AC, Roberts L, Caro I, Xue C, Wainstein A. First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. Pigment Cell Melanoma Res. 2021;34(5):973-977. doi:10.1111/pcmr.12960
22. Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(11):1480-1492. doi:10.1016/S1470-2045(18)30700-9
23. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J Clin Oncol Off J Am Soc Clin Oncol. 2022;40(2):127-137. doi:10.1200/JCO.21.02229
24. Daud AI, Wolchok JD, Robert C, et al. Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(34):4102-4109. doi:10.1200/JCO.2016.67.2477
25. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022;386(1):24-34. doi:10.1056/NEJMoa2109970
26. Long GV, Stephen Hodi F, Lipson EJ, et al. Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma. NEJM Evid. 2023;2(4):EVIDoa2200239. doi:10.1056/EVIDoa2200239
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