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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2018

01-07-2018 | Melanomas

Adjuvant Therapy in the Treatment of Melanoma

Authors: Danielle M. Bello, MD, Charlotte E. Ariyan, MD, PhD

Published in: Annals of Surgical Oncology | Issue 7/2018

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Excerpt

Melanoma is an aggressive form of cutaneous malignancy, with over 10,000 deaths in the US in 2016.1 In the past 10 years, treatment for stage IV disease with targeted therapy and immune therapy has changed the trajectory of the disease. While the median survival of patients with stage IV disease was historically < 1 year, there are now patients alive without disease recurrence for more than 10 years. The successful treatment of stage IV patients raises the question as to whether patients with high-risk features (stage II or III) can be administered the treatment in a ‘prophylactic’ or ‘adjuvant’ setting in order to prevent disease recurrence and treat micrometastatic disease. Immunotherapy has been the most tested adjuvant therapy in melanoma and will be the focus of this review. …
Literature
1.
2.
Dawson JW, Taylor I. Principles of adjuvant therapy. Br J Hosp Med. 1995;54:249–54.PubMed
3.
Callender GG, Gershenwald JE, Egger ME, et al. A novel and accurate computer model of melanoma prognosis for patients staged by sentinel lymph node biopsy: comparison with the American Joint Committee on Cancer model. J Am Coll Surg. 2012;214:608–17, discussion 17–9.CrossRefPubMed
4.
Tanabe KK, Jara S, Michaelson J. Creating and providing predictions of melanoma outcome. Ann Surg Oncol. 2010;17:1981–2.CrossRefPubMed
5.
Soong SJ, Ding S, Coit D, et al. Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC Melanoma Database. Ann Surg Oncol. 2010;17:2006–14.CrossRefPubMed
6.
Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–92.CrossRefPubMedPubMedCentral
7.
Gerami P, Cook RW, Wilkinson J, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015;21:175–83.CrossRefPubMed
8.
Clarke LE, Warf MB, Flake DD, 2nd, et al. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol. 2015;42:244–52.CrossRefPubMed
9.
Meves A, Nikolova E, Heim JB, et al. Tumor cell adhesion as a risk factor for sentinel lymph node metastasis in primary cutaneous melanoma. J Clin Oncol. 2015;33:2509–15.CrossRefPubMedPubMedCentral
10.
Brunner G, Reitz M, Heinecke A, et al. A nine-gene signature predicting clinical outcome in cutaneous melanoma. J Cancer Res Clin Oncol. 2013;139:249–58.CrossRefPubMed
11.
Gerami P, Cook RW, Russell MC, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. 2015;72:780–5CrossRefPubMed
12.
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.CrossRefPubMed
13.
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.CrossRefPubMedPubMedCentral
14.
15.
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;14:7–17.CrossRefPubMed
16.
Chiarion-Sileni V, Del Bianco P, Romanini A, et al. Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI—Mel.A.) [ISRCTN75125874]. BMC Cancer. 2006;6:44.CrossRefPubMedPubMedCentral
17.
Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. 2000;18:2444–58.CrossRefPubMed
18.
Kirkwood JM, Ibrahim JG, Sosman JA, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. 2001;19:2370–80.CrossRefPubMed
19.
Agarwala SS, Lee SJ, Yip W, et al. Phase III Randomized Study of 4 weeks of high-dose interferon-alpha-2b in Stage T2bNO, phase III randomized study of 4 weeks of high-dose interferon-alpha-2b in stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) melanoma: a trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697). J Clin Oncol. 2017;35:885–92.CrossRefPubMedPubMedCentral
20.
Grob JJ, Dreno B, de la Salmoniere P, French Cooperative Group on Melanoma, et al. Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. Lancet. 1998;351:1905–10.CrossRefPubMed
21.
Pehamberger H, Soyer HP, Steiner A, Austrian Malignant Melanoma Cooperative Group et al. Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. J Clin Oncol. 1998;16:1425–9.CrossRefPubMed
22.
Cascinelli N, Bufalino R, Morabito A, Mackie R. Results of adjuvant interferon study in WHO melanoma programme. Lancet. 1994;343:913–4.CrossRefPubMed
23.
Hancock BW, Wheatley K, Harris S, et al. Adjuvant interferon in high-risk melanoma: the AIM HIGH Study—United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma. J Clin Oncol. 2004;22:53–61.CrossRefPubMed
24.
Kleeberg UR, Suciu S, Brocker EB, et al. Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness > 3 mm) or regional lymph node metastasis. Eur J Cancer. 2004;40:390–402.CrossRefPubMed
25.
Hauschild A, Weichenthal M, Rass K, 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;28:841–6.CrossRefPubMed
26.
Grob JJ, Jouary T, Dreno B, et al. Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macrometastatic nodes: an open-label, randomised, phase 3 European Association for Dermato-Oncology (EADO) study. Eur J Cancer. 2013;49:166–74.CrossRefPubMed
27.
Garbe C, Radny P, Linse R, et al. Adjuvant low-dose interferon α2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis. Ann Oncol. 2008;19:1195–201.CrossRefPubMed
28.
Eggermont AM, Suciu S, Santinami M, 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.CrossRefPubMed
29.
Eggermont AM, Spatz A, Lazar V, Robert C. Is ulceration in cutaneous melanoma just a prognostic and predictive factor or is ulcerated melanoma a distinct biologic entity? Curr Opin Oncol. 2012;24:137–40.CrossRefPubMed
30.
Eggermont AM, Suciu S, Testori A, 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;48:218–25.CrossRefPubMed
31.
Ives AM, Suciu S, Eggermont AMM, et al. Adjuvant interferon-alpha for the treatment of high-risk melanoma: An individual patient data meta-analysis. Eur J Cancer. 2017;82:171–83.CrossRef
32.
Bottomley A, Coens C, Suciu S, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol. 2009;27:2916–23.CrossRefPubMed
33.
34.
Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–26.CrossRefPubMed
35.
Maio M, Grob JJ, Aamdal S, et al. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol. 2015;33:1191–6.CrossRefPubMedPubMedCentral
36.
Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16:522–30.CrossRefPubMed
37.
Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375:1845–55.CrossRefPubMedPubMedCentral
38.
39.
Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol. 2010;37:508–16.CrossRefPubMed
40.
Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75.CrossRefPubMedPubMedCentral
41.
42.
Gibney GT, Kudchadkar RR, DeConti RC, et al. Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Clin Cancer Res. 2015;21:712–20.CrossRefPubMed
43.
Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377:1824–35.CrossRefPubMed
44.
Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:1270–1.CrossRefPubMed
45.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:1345–56.CrossRefPubMedPubMedCentral
46.
Menzies AM, Long GV, Murali R. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Dev Ther. 2012;6:391–405.
47.
Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386:444–51.CrossRefPubMed
48.
49.
Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1813–23.CrossRefPubMed
50.
Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371:1877–88.CrossRefPubMed
51.
Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9.CrossRefPubMed
52.
53.
Kohn CG, Zeichner SB, Chen Q, Montero AJ, Goldstein DA, Flowers CR. Cost-effectiveness of immune checkpoint inhibition in BRAF wild-type advanced melanoma. J Clin Oncol. 2017;35:1194–202.CrossRefPubMedPubMedCentral
54.
55.
Metadata
Title
Adjuvant Therapy in the Treatment of Melanoma
Authors
Danielle M. Bello, MD
Charlotte E. Ariyan, MD, PhD
Publication date
01-07-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 7/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6376-y

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