Skip to main content

Adjuvant Treatment of Melanoma: Recent Developments and Future Perspectives

Abstract

Surgical excision is the treatment of choice for early stage melanoma, and this strategy is initially curative for the vast majority of patients. However, only approximately 40–60% of high-risk patients who undergo surgery alone will be disease-free at 5 years. These patients will ultimately experience loco-regional relapse or relapse at distant sites. The main aim of adjuvant therapies is to reduce the recurrence rate of radically operated patients at high risk and to potentially improve survival. Recent practice changing results with immune checkpoint inhibitors and targeted therapies have been published in stage III/IV melanoma patients, after surgical complete resection, and have dramatically improved the landscape of adjuvant therapy. Interferon-α, ipilimumab, and more recently anti-programmed cell death protein-1 antibodies and BRAF inhibitors plus MEK inhibitors have been approved in the adjuvant setting by the US Food and Drug Administration; similarly, the same drugs are approved by the European Medicines Agency with the exception of ipilimumab. A completely new scenario is emerging in the neoadjuvant setting as well: in locally advanced or metastatic disease, patients may partially respond to neoadjuvant therapy and become virtually resectable with systemic control of disease. This review summarizes the current state of the field and describes new strategies tracing the history of adjuvant therapy in melanoma, with a view on future projects.

This is a preview of subscription content, access via your institution.

References

  1. Ribero S, Glass D, Bataille V. Genetic epidemiology of melanoma. Eur J Dermatology. 2016;26(4):335–9.

    CAS  Google Scholar 

  2. Testori A, De Salvo G, Montesco M, Trifiro’ G, Mocellin S, Landi G, et al. Clinical considerations on sentinel node biopsy in melanoma from Italian multicentric study on 1,313 patients (SOLISM-IMI). Ann Surg Oncol. 2009;16(7):2018–27.

    PubMed  Article  Google Scholar 

  3. Mandalà M, Galli F, Cattaneo L, Merelli B, Rulli E, Ribero S, et al. Mitotic rate correlates with sentinel lymph node status and outcome in cutaneous melanoma greater than 1 millimeter in thickness: A multi-institutional study of 1524 cases. J Am Acad Dermatol. 2017;76(2):264–73.

    PubMed  Article  Google Scholar 

  4. Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel node metastasis in melanoma. N Engl J Med. 2017;376:2211–22.

    PubMed  PubMed Central  Article  Google Scholar 

  5. Leiter U, Stadler R, Mauch C, et al. Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17:757–67.

    PubMed  Article  Google Scholar 

  6. Pasquali S, Mocellin S, Mozzillo N, Maurichi A, Quaglino P, Borgognoni L, et al. Nonsentinel lymph node status in patients with cutaneous melanoma: results from a multi-institution prognostic study. J Clin Oncol. 2014;32(9):935–41.

    PubMed  Article  Google Scholar 

  7. Pasquali S, Andrea M, Nicola M, Simone M, Giuseppe M, Lorenzo B, et al. Lymph-node ratio in patients with cutaneous melanoma: a multi-institution prognostic study. Ann Surg Oncol. 2015;22(7):2127–34.

    Article  Google Scholar 

  8. Rossi CR, Mocellin S, Campana LG, Borgognoni L, Sestini S, Giudice G, et al. Prediction of non-sentinel node status in patients with melanoma and positive sentinel node biopsy: an Italian Melanoma Intergroup (IMI) study. Ann Surg Oncol. 2018;25(1):271–9.

    PubMed  Article  Google Scholar 

  9. Verver D, van Klaveren D, van Akkooi ACJ, Rutkowski P, Powell BWEM, Robert C, et al. Risk stratification of sentinel node-positive melanoma patients defines surgical management and adjuvant therapy treatment considerations. Eur J Cancer. 2018;96:25–33.

    PubMed  Article  Google Scholar 

  10. Flaherty LE, Othus M, Atkins MB, Tuthill RJ, Thompson JA, Vetto JT, et al. Southwest Oncology Group S0008: a phase III trial of high-dose interferon alfa-2b versus cisplatin, vinblastine, and dacarbazine DTIC, plus interleukin-2 and interferon in patients with high-risk melanoma—an Intergroup Study of Cancer and Leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. J Clin Oncol. 2014;32(33):3771–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. Figlin RA, Thompson JA, Bukowski RM, Vogelzang NJ, Novick AC, Lange P, et al. Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol. 1999;17:2521–9.

    CAS  PubMed  Article  Google Scholar 

  12. Veronesi U, Adamus J, Aubert C, Bajetta E, Beretta G, Bonadonna G, et al. A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med. 1982;307:913–6.

    CAS  PubMed  Article  Google Scholar 

  13. Agarwala SS, Neuberg D, Park Y, Kirkwood JM. Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer stage I–III melanoma (E1673) A trial of the Eastern Cooperative Oncology Group. Cancer. 2004;100(8):1692–8.

    CAS  PubMed  Article  Google Scholar 

  14. Faries MB, Mozzillo N, Kashani-Sabet M, Thompson JF, Kelley MC, DeConti RC, et al. Long-term survival after complete surgical resection and adjuvant immunotherapy for distant melanoma metastases. Ann Surg Oncol. 2017;24:3991–4000.

    PubMed  Article  Google Scholar 

  15. Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol. 2015;15(7):405–14.

    CAS  PubMed  Article  Google Scholar 

  16. Raig ET, Jones NB, Varker KA, Benniger K, Go MR, Biber JL, et al. VEGF secretion is inhibited by interferon-alpha in several melanoma cell lines. J Interferon Cytokine Res. 2008;28(9):553–61.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Palmer KJ, Harries M, Gore ME, Collins MK. Interferon-alpha (IFN-alpha) stimulates anti-melanoma cytotoxic T lymphocyte (CTL) generation in mixed lymphocyte tumour cultures (MLTC). Clin Exp Immunol. 2000;119(3):412–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996;14(1):7–17.

    CAS  PubMed  Article  Google Scholar 

  19. Hauschild A, Weichenthal M, Rass K, Linse R, Ulrich J, Stadler R, et al. Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma. J Clin Oncol. 2009;27(21):3496–502.

    CAS  PubMed  Article  Google Scholar 

  20. Kirkwood JM, Ibrahim JG, Sondak VK, Richards J, Flaherty LE, Ernstoff MS, et al. High- and low-dose interferon α-2b in high-risk melanoma: first analysis of Intergroup Trial E1690/S9111/C9190. J Clin Oncol. 2000;18:2444–58.

    CAS  PubMed  Article  Google Scholar 

  21. Hauschild A, Weichenthal M, Rass K, Linse R, Berking C, Böttjer J, et al. Efficacy of low-dose interferon α2a 18 versus 60 months of treatment in patients with primary melanoma of ≥ 1.5 mm tumor thickness: results of a randomized phase III DeCOG trial. J Clin Oncol. 2010;28(5):841–6.

    CAS  PubMed  Article  Google Scholar 

  22. Eggermont AM, Suciu S, Rutkowski P, Kruit WH, Punt CJ, Dummer R, et al. Long term follow up of the EORTC 18952 trial of adjuvant therapy in resected stage IIB-III cutaneous melanoma patients comparing intermediate doses of interferon-alpha-2b (IFN) with observation: Ulceration of primary is key determinant for IFN-sensitivity. Eur J Cancer. 2016;55:111–21.

    CAS  PubMed  Article  Google Scholar 

  23. Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2010;102(7):493–501.

    CAS  PubMed  Article  Google Scholar 

  24. Wheatley K, Ives NJ, Hancock B, Gore M, Eggermont A, Suciu S. Does adjuvant interferon-α for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev. 2003;29:241–52.

    CAS  PubMed  Article  Google Scholar 

  25. Ives NJ, Suciu S, Eggermont AMM, Kirkwood J, Lorigan P, Markovic SN, et al. Adjuvant interferon-α for the treatment of high-risk melanoma: an individual patient data meta-analysis. Eur J Cancer. 2017;82:171–83.

    CAS  PubMed  Article  Google Scholar 

  26. Eggermont AM, Suciu S, Testori A, Santinami M, Kruit WH, Marsden J, et al. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J Clin Oncol. 2012;30(31):3810–8.

    CAS  PubMed  Article  Google Scholar 

  27. Eggermont AM, Suciu S, Testori A, Kruit WH, Marsden J, Punt CJ, et al. Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer. 2012;48(2):218–25.

    CAS  PubMed  Article  Google Scholar 

  28. Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008;372:117–26.

    CAS  PubMed  Article  Google Scholar 

  29. Stockwin LH, McGonagle D, Martin IG, Blair GE. Dendritic cells: immunological sentinels with a central role in health and disease. Immunol Cell Biol. 2000;78(2):91–102.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  30. Nencioni A, Grünebach F, Schmidt SM, Müller MR, Boy D, Patrone F, et al. The use of dendritic cells in cancer immunotherapy. Crit Rev Oncol Hematol. 2008;65(3):191–9.

    PubMed  Article  Google Scholar 

  31. Boudewijns S, Bol KF, Schreibelt G, Westdorp H, Textor JC, van Rossum MM, et al. Adjuvant dendritic cell vaccination induces tumor specific immune responses in the majority of stage III melanoma patients. Oncoimmunology. 2016;5(7):e1191732.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  32. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.

    CAS  Article  PubMed  Google Scholar 

  33. Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, et al. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015;348(6236):803–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Delamarre L, Mellman I, Yadav M. Cancer immunotherapy. Neo approaches to cancer vaccines. Science. 2015;348(6236):760–1.

    CAS  PubMed  Article  Google Scholar 

  35. Dreno B, Thompson JF, Smithers BM, Santinami M, Jouary T, Gutzmer R, et al. MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(7):916–29.

    CAS  PubMed  Article  Google Scholar 

  36. Saiag P, Gutzmer R, Ascierto PA, Maio M, Grob JJ, Murawa P, et al. Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT). Ann Oncol. 2016;27(10):1947–53.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Corrie PG, Marshall A, Dunn JA, Middleton MR, Nathan PD, Gore M, et al. Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study. Lancet Oncol. 2014;15(6):620–30.

    CAS  PubMed  Article  Google Scholar 

  38. Bastiaannet E, Beukema JC, Hoekstra HJ. Radiation therapy following lymph node dissection in melanoma patients: treatment, outcome and complications. Cancer Treat Rev. 2005;31(1):18–26.

    CAS  PubMed  Article  Google Scholar 

  39. Keenan LG, O’Sullivan S, Glynn A, Higgins M, Flavin A, Brennan S. Clinical review of treatment outcomes and patterns of failure with adjuvant radiotherapy in node-positive malignant melanoma. J Med Imaging Radiat Oncol. 2017;61(2):258–62.

    PubMed  Article  Google Scholar 

  40. Strom T, Torres-Roca JF, Parekh A, Naghavi AO, Caudell JJ, Oliver DE, et al. Regional radiation therapy impacts outcome for node-positive cutaneous melanoma. J Natl Compr Cancer Netw. 2017;15(4):473–82.

    Article  Google Scholar 

  41. Moncrieff MD, Martin R, O’Brien CJ, Shannon KF, Clark JR, Gao K, et al. Adjuvant postoperative radiotherapy to the cervical lymph nodes in cutaneous melanoma: is there any benefit for high-risk patients? Ann Surg Oncol. 2008;15(11):3022–7.

    PubMed  Article  Google Scholar 

  42. Ribero S, Longo C, Glass D, Nathan P, Bataille V. What is new in melanoma genetics and treatment? Dermatology. 2016;232(3):259–64.

    CAS  PubMed  Article  Google Scholar 

  43. Eggermont AMM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375:1845–55.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Weber JS, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–35.

    CAS  PubMed  Article  Google Scholar 

  45. Weber JS, Mandalà M, Del Vecchio M, Gogas H, Arance AM, et al. Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: updated results from a phase III trial (CheckMate 238). J Clin Oncol. 2018;36(suppl):abstr 9502.

    Article  Google Scholar 

  46. Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378:1789–801.

    CAS  PubMed  Article  Google Scholar 

  47. Grossmann, KF Othus M, Tarhini AA, Patel SP, Moon J, Sondak VK, et al. SWOG S1404: a phase III randomized trial comparing standard of care adjuvant therapy to pembrolizumab in patients with high risk resected melanoma. In: ASCO annual meeting. 2017. abstract e21032.

  48. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.

    CAS  PubMed  Article  Google Scholar 

  49. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(11):1087–95.

    CAS  PubMed  Article  Google Scholar 

  51. 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;494(7436):251–5.

    CAS  PubMed  Article  Google Scholar 

  52. Trunzer K, Pavlick AC, Schuchter L, Gonzalez R, McArthur GA, Hutson TE, et al. Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol. 2013;31:1767–74.

    CAS  PubMed  Article  Google Scholar 

  53. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877–88.

    PubMed  Article  CAS  Google Scholar 

  54. Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867–76.

    PubMed  Article  CAS  Google Scholar 

  55. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107–14.

    CAS  PubMed  Article  Google Scholar 

  56. Maio M, Lewis K, Demidov L, Mandalà M, Bondarenko I, Ascierto PA, et al. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2018;19(4):510–20.

    CAS  PubMed  Article  Google Scholar 

  57. Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377(19):1813–23.

    CAS  PubMed  Article  Google Scholar 

  58. Hauschild A, Dummer R, Schadendorf D, Santinami M, Atkinson V, Mandalà M, et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant stage III melanoma. J Clin Oncol. 2018;36:3441–9.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  59. Mandalà M, De Logu F, Merelli B, Nassini R, Massi D. Immunomodulating property of MAPK inhibitors: from translational knowledge to clinical implementation. Lab Invest. 2017;97(2):166–75.

    PubMed  Article  CAS  Google Scholar 

  60. Liu J, Blake SJ, Yong MC, Harjunpää H, Ngiow SF, Takeda K, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 2016;6(12):1382–99.

    CAS  PubMed  Article  Google Scholar 

  61. Amaria RN, Prieto PA, Tetzlaff MT, Reuben A, Andrews MC, Ross MI, et al. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol. 2018;19(2):181–93.

    CAS  PubMed  Article  Google Scholar 

  62. Blankenstein S, Rohaan MW, Klop WMC, van der Hiel B, van de Wiel B, Peeper D, et al. Neoadjuvant cytoreductive treatment of regionally advanced melanoma with BRAF/MEK inhibition: study protocol of the REDUCTOR (Cytoreductive Treatment of Dabrafenib Combined With Trametinib to Allow Complete Surgical Resection in Patients With BRAF Mutated, Prior Unresectable Stage III or IV Melanoma). Ann Oncol 2018;29(suppl_8):viii442–viii466. https://doi.org/10.1093/annonc/mdy289.

  63. Blank CU, Rozeman EA, Fanchi LF, Sikorska K, van de Wiel B, Kvistborg P, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24(11):1655–61.

    CAS  PubMed  Article  Google Scholar 

  64. Rozeman EA, Menzies AM, van de Wielk BA, Adhikari C, Sikorska K, Krijgsman O, et al. Opacin-neo: a multicenter phase 2 study to identify the optimal neo-adjuvant combination scheme of ipilimumab and nivolumab. In: ESMO congress 2018, abstract. https://doi.org/10.1200/jco.2017.35.15_suppl.tps9600(Journal of Clinical Oncology 35(15_suppl)).

    Article  Google Scholar 

  65. Madu MF, Schopman JHH, Berger DMS, Klop WMC, Jóźwiak K, Wouters MWJM, et al. Clinical prognostic markers in stage IIIC melanoma. J Surg Oncol. 2017;116(2):244–51.

    CAS  PubMed  Article  Google Scholar 

  66. Davis JL, Langan RC, Panageas KS, Zheng J, Postow MA, Brady MS, et al. Elevated blood neutrophil-to-lymphocyte ratio: a readily available biomarker associated with death due to disease in high risk nonmetastatic melanoma. Ann Surg Oncol. 2017;24(7):1989–96.

    PubMed  PubMed Central  Article  Google Scholar 

  67. Tarhini A, Kudchadkar RR. Predictive and on-treatment monitoring biomarkers in advanced melanoma: moving toward personalized medicine. Cancer Treat Rev. 2018;71:8–18.

    CAS  PubMed  Article  Google Scholar 

  68. Sivendran S, Chang R, Pham L, Phelps RG, Harcharik ST, Hall LD, et al. Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II–III resectable disease. J Invest Dermatol. 2014;134(8):2202–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. Gerami P, Cook RW, Wilkinson J, Russell MC, Dhillon N, Amaria RN, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015;21(1):175–83.

    CAS  PubMed  Article  Google Scholar 

  70. Zager JS, Gastman BR, Leachman S, Gonzalez RC, Fleming MD, Ferris LK, et al. Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer. 2018;18(1):130.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  71. Gray ES, Rizos H, Reid AL, Boyd SC, Pereira MR, Lo J, et al. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget. 2015;6(39):42008–18.

    PubMed  PubMed Central  Article  Google Scholar 

  72. Lee RJ, Gremel G, Marshall A, Myers KA, Fisher N, Dunn JA, et al. Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma. Ann Oncol. 2018;29(2):490–6.

    CAS  PubMed  Article  Google Scholar 

  73. Marconcini R, Spagnolo F, Stucci LS, Ribero S, Marra E, De Rosa F, et al. Current status and perspectives in immunotherapy for metastatic melanoma. Oncotarget. 2018;9(15):12452–70.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alessandro A. E. Testori.

Ethics declarations

Funding

This paper did not receive any economic support. No external funding was used in the preparation of this manuscript.

Conflict of interest

Alessandro Testori, Simone Ribero, Alice Indini, and Mario Mandalà declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Testori, A.A.E., Ribero, S., Indini, A. et al. Adjuvant Treatment of Melanoma: Recent Developments and Future Perspectives. Am J Clin Dermatol 20, 817–827 (2019). https://doi.org/10.1007/s40257-019-00456-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-019-00456-4