The adjuvant treatment revolution for high-risk melanoma patients: Seminars in Cancer Biology

F. Spagnolo; A. Boutros; E. Tanda; P. Queirolo

doi:10.1016/j.semcancer.2019.08.024

The adjuvant treatment revolution for high-risk melanoma patients: Seminars in Cancer Biology

F. Spagnolo, A. Boutros, E. Tanda, P. Queirolo

Research output: Contribution to journal › Article

Abstract

The past 5 years have witnessed the results of many practice-changing studies that have dramatically improved the landscape of adjuvant therapy in patients with resected, high-risk melanoma. After a 20-year era of adjuvant interferon, the anti-CTLA-4 and anti-PD-1 immune-checkpoint inhibitors, and MAPK-directed targeted therapy brought a revolution into the adjuvant treatment of melanoma. These results came along with the practice-changing results of two large multicenter studies showing no benefit in terms of overall survival for completion lymph node dissection after positive sentinel node biopsy. In this review, we summarized the current state of the art of the adjuvant treatment of high-risk melanoma, with a view on future perspectives. © 2019

Original language	English
Pages (from-to)	283-289
Number of pages	7
Journal	Semin. Cancer Biol.
Volume	59
DOIs	https://doi.org/10.1016/j.semcancer.2019.08.024
Publication status	Published - 2019

Keywords

Adjuvant
Immunotherapy
Melanoma
Neoadjuvant
Targeted therapy
alpha interferon
bevacizumab
dabrafenib
ipilimumab
nivolumab
pembrolizumab
trametinib
vemurafenib
adjuvant therapy
cancer staging
colitis
disease classification
distant metastasis free survival
drug efficacy
drug tolerability
fatigue
fever
Guillain Barre syndrome
high risk patient
human
lymph node dissection
lymph node metastasis
melanoma
myocarditis
nausea
overall survival
recurrence free survival
Review

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10.1016/j.semcancer.2019.08.024

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Spagnolo, F., Boutros, A., Tanda, E., & Queirolo, P. (2019). The adjuvant treatment revolution for high-risk melanoma patients: Seminars in Cancer Biology. Semin. Cancer Biol., 59, 283-289. https://doi.org/10.1016/j.semcancer.2019.08.024

@article{e5e3e4fe934041d89c37d599b7713aef,

title = "The adjuvant treatment revolution for high-risk melanoma patients: Seminars in Cancer Biology",

abstract = "The past 5 years have witnessed the results of many practice-changing studies that have dramatically improved the landscape of adjuvant therapy in patients with resected, high-risk melanoma. After a 20-year era of adjuvant interferon, the anti-CTLA-4 and anti-PD-1 immune-checkpoint inhibitors, and MAPK-directed targeted therapy brought a revolution into the adjuvant treatment of melanoma. These results came along with the practice-changing results of two large multicenter studies showing no benefit in terms of overall survival for completion lymph node dissection after positive sentinel node biopsy. In this review, we summarized the current state of the art of the adjuvant treatment of high-risk melanoma, with a view on future perspectives. {\textcopyright} 2019",

keywords = "Adjuvant, Immunotherapy, Melanoma, Neoadjuvant, Targeted therapy, alpha interferon, bevacizumab, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib, vemurafenib, adjuvant therapy, cancer staging, colitis, disease classification, distant metastasis free survival, drug efficacy, drug tolerability, fatigue, fever, Guillain Barre syndrome, high risk patient, human, lymph node dissection, lymph node metastasis, melanoma, myocarditis, nausea, overall survival, recurrence free survival, Review",

author = "F. Spagnolo and A. Boutros and E. Tanda and P. Queirolo",

note = "Cited By :2 Export Date: 2 March 2020 CODEN: SECBE Correspondence Address: Queirolo, P.; Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCSItaly; email: paola.queirolo@hsanmartino.it Chemicals/CAS: bevacizumab, 216974-75-3, 1438851-35-4; dabrafenib, 1195765-45-7, 1195768-06-9; ipilimumab, 477202-00-9; nivolumab, 946414-94-4; pembrolizumab, 1374853-91-4; trametinib, 1187431-43-1, 871700-17-3; vemurafenib, 918504-65-1 References: Gershenwald, J.E., Scolyer, R.A., Hess, K.R., Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual: melanoma Staging: AJCC 8 th Edition (2017) CA Cancer J. Clin., 67 (6), pp. 472-492; Leiter, U., Stadler, R., Mauch, C., Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: a multicenter, randomized DECOG trial (2015) J. Clin. Oncol., 33 (18_suppl). , LBA9002–LBA9002; Leiter, U., Stadler, R., Mauch, C., Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial (2016) Lancet Oncol., 17 (6), pp. 757-767; Faries, M.B., Thompson, J.F., Cochran, A.J., Completion dissection or observation for sentinel-node metastasis in melanoma (2017) N. Engl. J. Med., 376 (23), pp. 2211-2222; Amin, M.B., Greene, F.L., Edge, S.B., The Eighth Edition AJCC Cancer staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging (2017) CA Cancer J. Clin., 67 (2), pp. 93-99; Morton, D.L., Thompson, J.F., Cochran, A.J., Final trial report of sentinel-node biopsy versus nodal observation in melanoma (2014) N. Engl. J. Med., 370 (7), pp. 599-609; Thompson, J.F., Haydu, L.E., Uren, R.F., Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results from a Large Multicenter Trial Ann. Surg, , 9000; Leiter, U.M., Stadler, R., Mauch, C., Final analysis of DECOG-SLT trial: survival outcomes of complete lymph node dissection in melanoma patients with positive sentinel node (2018) J. Clin. Oncol., 36 (15_suppl). , 9501–9501; van Akkooi, A.C.J., Nowecki, Z.I., Voit, C., Sentinel node tumor burden according to the rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes (2008) Ann. Surg., 248 (6), pp. 949-955; Coit, D., The enigma of regional lymph nodes in melanoma (2017) N. Engl. J. Med., 376 (23), pp. 2280-2281; Coit, D.G., Thompson, J.A., Albertini, M.R., Cutaneous melanoma, version 2.2019, NCCN clinical practice guidelines in oncology (2019) J. Natl. Compr. Cancer Netw. J Natl Compr Canc Netw, 17 (4), pp. 367-402; Kirkwood, J.M., Strawderman, M.H., Ernstoff, M.S., Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684 (1996) J. Clin. Oncol., 14 (1), pp. 7-17; Grob, J.J., Dreno, B., de la Salmoniere, P., Randomised trial of interferon α-2a as adjuvant therapy in resected primary melanoma thicker than 1·5 mm without clinically detectable node metastases (1998) Lancet, 351 (9120), pp. 1905-1910; Eggermont, A.M., Suciu, S., Santinami, M., 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 (2008) Lancet, 372 (9633), pp. 117-126; Mocellin, S., Lens, M.B., Pasquali, S., Interferon alpha for the adjuvant treatment of cutaneous melanoma (2013) Cochrane Database Syst. Rev.; Ives, N.J., Suciu, S., Eggermont, A.M.M., Adjuvant interferon-α for the treatment of high-risk melanoma: an individual patient data meta-analysis (2017) Eur. J. Cancer, 82, pp. 171-183; Corrie, P.G., Marshall, A., Nathan, P.D., Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial (2018) Ann. Oncol. Off. J. Eur. Soc. Med. Oncol, 29 (8), pp. 1843-1852; Grob, J.-J., Mortier, L., D'Hondt, L., Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II study with a first assessment of a predictive gene signature (2017) ESMO Open, 2 (5); Eggermont, A.M.M., Chiarion-Sileni, V., Grob, J.-J., Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial (2015) Lancet Oncol., 16 (5), pp. 522-530; Eggermont, A.M.M., Chiarion-Sileni, V., Grob, J.-J., Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy (2016) N. Engl. J. Med., 375 (19), pp. 1845-1855; Tarhini, A.A., Lee, S.J., Hodi, F.S., A phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk melanoma (U.S. Intergroup E1609): preliminary safety and efficacy of the ipilimumab arms (2017) J. Clin. Oncol., 35 (15_suppl). , 9500–9500; Tarhini, A.A., Lee, S.J., Hodi, F.S., United States Intergroup E1609: a phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon-α2b for resected high-risk melanoma (2019) J. Clin. Oncol., 37 (15_suppl). , 9504–9504; Robert, C., Ribas, A., Schachter, J., 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; Hodi, F.S., Chiarion-Sileni, V., Gonzalez, R., Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial (2018) Lancet Oncol., 19 (11), pp. 1480-1492; Weber, J., Mandala, M., Del Vecchio, M., Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma (2017) N. Engl. J. Med., 377 (19), pp. 1824-1835; Weber, J.S., Mandal{\`a}, M., Del Vecchio, M., 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) (2018) J. Clin. Oncol., 36 (15_suppl). , 9502–9502; Eggermont, A.M.M., A. Adjuvant pembrolizumab in resected stage III melanoma (2018) N. Engl. J. Med., 379 (6), pp. 593-595; Suciu, S., Eggermont, A.M.M., Lorigan, P., Relapse-free survival as a surrogate for overall survival in the evaluation of stage II–III melanoma adjuvant therapy (2017) JNCI J. Natl. Cancer Inst., 110 (1), pp. 87-96; Davies, H., Bignell, G.R., Cox, C., Mutations of the BRAF gene in human cancer (2002) Nature, 417, p. 949; McArthur, G.A., Chapman, P.B., Robert, C., Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study (2014) Lancet Oncol., 15 (3), pp. 323-332; Hauschild, A., Grob, J.-J., Demidov, L.V., Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial (2012) Lancet, 380 (9839), pp. 358-365; Robert, C., Grob, J.J., Stroyakovskiy, D., Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma (2019) N. Engl. J. Med.; Ascierto, P.A., McArthur, G.A., Dr{\'e}no, B., Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial (2016) Lancet Oncol., 17 (9), pp. 1248-1260; Dummer, R., Ascierto, P.A., Gogas, H.J., Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial (2018) Lancet Oncol., 19 (10), pp. 1315-1327; Maio, M., Lewis, K., Demidov, L., Adjuvant vemurafenib in resected, BRAF V600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial (2018) Lancet Oncol., 19 (4), pp. 510-520; Long, G.V., Hauschild, A., Santinami, M., Adjuvant Dabrafenib plus Trametinib in Stage IIIBRAF -Mutated Melanoma (2017) N. Engl. J. Med., 377 (19), pp. 1813-1823; Hauschild, A., Dummer, R., Schadendorf, D., Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-Mutant stage III melanoma (2018) J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol., p. JCO1801219; Long, G.V., Stroyakovskiy, D., Gogas, H., Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial (2015) Lancet Lond. Engl, 386 (9992), pp. 444-451; Robert, C., Karaszewska, B., Schachter, J., Improved overall survival in melanoma with combined dabrafenib and trametinib (2014) N. Engl. J. Med., 372 (1), pp. 30-39; Schadendorf, D., Hauschild, A., Santinami, M., Effect on health-related quality of life (HRQOL) of adjuvant treatment (tx) with dabrafenib plus trametinib (D + T) in patients (pts) with resected stage III BRAF-mutant melanoma (2018) J. Clin. Oncol., 36 (15_suppl). , 9590–9590; Long, G.V., Flaherty, K.T., Stroyakovskiy, D., 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 (2017) Ann. Oncol. Off. J. Eur. Soc. Med. Oncol, 28 (7), pp. 1631-1639; Robert, C., Karaszewska, B., Schachter, J., Three-year estimate of overall survival in COMBI-v, a randomized phase 3 study evaluating first-line dabrafenib (D) + trametinib (T) in patients (pts) with unresectable or metastatic BRAF V600E/K–mutant cutaneous melanoma (2016) Ann. Oncol.; Verver, D., van Klaveren, D., van Akkooi, A.C.J., Risk stratification of sentinel node–positive melanoma patients defines surgical management and adjuvant therapy treatment considerations (2018) Eur. J. Cancer, 96, pp. 25-33; Balch, C.M., Gershenwald, J.E., Soong, S.-J., Final version of 2009 AJCC melanoma staging and classification (2009) J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol, 27 (36), pp. 6199-6206; Blank, C.U., Rozeman, E.A., Fanchi, L.F., Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (2018) Nat. Med., 24 (11), pp. 1655-1661; Amaria, R.N., Reddy, S.M., Tawbi, H.A., Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma (2018) Nat. Med., 24 (11), pp. 1649-1654; Rozeman, E.A., Menzies, A.M., van Akkooi, A.C.J., 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 (2019) Lancet Oncol., 20 (7), pp. 948-960; Amaria, R.N., Prieto, P.A., Tetzlaff, M.T., 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 (2018) Lancet Oncol., 19 (2), pp. 181-193; Long, G.V., Saw, R.P.M., Lo, S., Neoadjuvant dabrafenib combined with trametinib for resectable, stage IIIB–C, BRAFV600 mutation-positive melanoma (NeoCombi): a single-arm, open-label, single-centre, phase 2 trial (2019) Lancet Oncol., 20 (7), pp. 961-971; Amaria, R.N., Menzies, A.M., Burton, E.M., Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium (2019) Lancet Oncol., 20 (7), pp. e378-e389",

year = "2019",

doi = "10.1016/j.semcancer.2019.08.024",

language = "English",

volume = "59",

pages = "283--289",

journal = "Semin. Cancer Biol.",

issn = "1044-579X",

publisher = "Academic Press",

}

TY - JOUR

T1 - The adjuvant treatment revolution for high-risk melanoma patients

T2 - Seminars in Cancer Biology

AU - Spagnolo, F.

AU - Boutros, A.

AU - Tanda, E.

AU - Queirolo, P.

N1 - Cited By :2 Export Date: 2 March 2020 CODEN: SECBE Correspondence Address: Queirolo, P.; Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCSItaly; email: paola.queirolo@hsanmartino.it Chemicals/CAS: bevacizumab, 216974-75-3, 1438851-35-4; dabrafenib, 1195765-45-7, 1195768-06-9; ipilimumab, 477202-00-9; nivolumab, 946414-94-4; pembrolizumab, 1374853-91-4; trametinib, 1187431-43-1, 871700-17-3; vemurafenib, 918504-65-1 References: Gershenwald, J.E., Scolyer, R.A., Hess, K.R., Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual: melanoma Staging: AJCC 8 th Edition (2017) CA Cancer J. Clin., 67 (6), pp. 472-492; Leiter, U., Stadler, R., Mauch, C., Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: a multicenter, randomized DECOG trial (2015) J. Clin. Oncol., 33 (18_suppl). , LBA9002–LBA9002; Leiter, U., Stadler, R., Mauch, C., Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial (2016) Lancet Oncol., 17 (6), pp. 757-767; Faries, M.B., Thompson, J.F., Cochran, A.J., Completion dissection or observation for sentinel-node metastasis in melanoma (2017) N. Engl. J. Med., 376 (23), pp. 2211-2222; Amin, M.B., Greene, F.L., Edge, S.B., The Eighth Edition AJCC Cancer staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging (2017) CA Cancer J. Clin., 67 (2), pp. 93-99; Morton, D.L., Thompson, J.F., Cochran, A.J., Final trial report of sentinel-node biopsy versus nodal observation in melanoma (2014) N. Engl. J. Med., 370 (7), pp. 599-609; Thompson, J.F., Haydu, L.E., Uren, R.F., Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results from a Large Multicenter Trial Ann. Surg, , 9000; Leiter, U.M., Stadler, R., Mauch, C., Final analysis of DECOG-SLT trial: survival outcomes of complete lymph node dissection in melanoma patients with positive sentinel node (2018) J. Clin. Oncol., 36 (15_suppl). , 9501–9501; van Akkooi, A.C.J., Nowecki, Z.I., Voit, C., Sentinel node tumor burden according to the rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes (2008) Ann. Surg., 248 (6), pp. 949-955; Coit, D., The enigma of regional lymph nodes in melanoma (2017) N. Engl. J. Med., 376 (23), pp. 2280-2281; Coit, D.G., Thompson, J.A., Albertini, M.R., Cutaneous melanoma, version 2.2019, NCCN clinical practice guidelines in oncology (2019) J. Natl. Compr. Cancer Netw. J Natl Compr Canc Netw, 17 (4), pp. 367-402; Kirkwood, J.M., Strawderman, M.H., Ernstoff, M.S., Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684 (1996) J. Clin. Oncol., 14 (1), pp. 7-17; Grob, J.J., Dreno, B., de la Salmoniere, P., Randomised trial of interferon α-2a as adjuvant therapy in resected primary melanoma thicker than 1·5 mm without clinically detectable node metastases (1998) Lancet, 351 (9120), pp. 1905-1910; Eggermont, A.M., Suciu, S., Santinami, M., 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 (2008) Lancet, 372 (9633), pp. 117-126; Mocellin, S., Lens, M.B., Pasquali, S., Interferon alpha for the adjuvant treatment of cutaneous melanoma (2013) Cochrane Database Syst. Rev.; Ives, N.J., Suciu, S., Eggermont, A.M.M., Adjuvant interferon-α for the treatment of high-risk melanoma: an individual patient data meta-analysis (2017) Eur. J. Cancer, 82, pp. 171-183; Corrie, P.G., Marshall, A., Nathan, P.D., Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial (2018) Ann. Oncol. Off. J. Eur. Soc. Med. Oncol, 29 (8), pp. 1843-1852; Grob, J.-J., Mortier, L., D'Hondt, L., Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II study with a first assessment of a predictive gene signature (2017) ESMO Open, 2 (5); Eggermont, A.M.M., Chiarion-Sileni, V., Grob, J.-J., Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial (2015) Lancet Oncol., 16 (5), pp. 522-530; Eggermont, A.M.M., Chiarion-Sileni, V., Grob, J.-J., Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy (2016) N. Engl. J. Med., 375 (19), pp. 1845-1855; Tarhini, A.A., Lee, S.J., Hodi, F.S., A phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk melanoma (U.S. Intergroup E1609): preliminary safety and efficacy of the ipilimumab arms (2017) J. Clin. Oncol., 35 (15_suppl). , 9500–9500; Tarhini, A.A., Lee, S.J., Hodi, F.S., United States Intergroup E1609: a phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon-α2b for resected high-risk melanoma (2019) J. Clin. Oncol., 37 (15_suppl). , 9504–9504; Robert, C., Ribas, A., Schachter, J., 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; Hodi, F.S., Chiarion-Sileni, V., Gonzalez, R., Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial (2018) Lancet Oncol., 19 (11), pp. 1480-1492; Weber, J., Mandala, M., Del Vecchio, M., Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma (2017) N. Engl. J. Med., 377 (19), pp. 1824-1835; Weber, J.S., Mandalà, M., Del Vecchio, M., 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) (2018) J. Clin. Oncol., 36 (15_suppl). , 9502–9502; Eggermont, A.M.M., A. Adjuvant pembrolizumab in resected stage III melanoma (2018) N. Engl. J. Med., 379 (6), pp. 593-595; Suciu, S., Eggermont, A.M.M., Lorigan, P., Relapse-free survival as a surrogate for overall survival in the evaluation of stage II–III melanoma adjuvant therapy (2017) JNCI J. Natl. Cancer Inst., 110 (1), pp. 87-96; Davies, H., Bignell, G.R., Cox, C., Mutations of the BRAF gene in human cancer (2002) Nature, 417, p. 949; McArthur, G.A., Chapman, P.B., Robert, C., Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study (2014) Lancet Oncol., 15 (3), pp. 323-332; Hauschild, A., Grob, J.-J., Demidov, L.V., Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial (2012) Lancet, 380 (9839), pp. 358-365; Robert, C., Grob, J.J., Stroyakovskiy, D., Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma (2019) N. Engl. J. Med.; Ascierto, P.A., McArthur, G.A., Dréno, B., Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial (2016) Lancet Oncol., 17 (9), pp. 1248-1260; Dummer, R., Ascierto, P.A., Gogas, H.J., Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial (2018) Lancet Oncol., 19 (10), pp. 1315-1327; Maio, M., Lewis, K., Demidov, L., Adjuvant vemurafenib in resected, BRAF V600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial (2018) Lancet Oncol., 19 (4), pp. 510-520; Long, G.V., Hauschild, A., Santinami, M., Adjuvant Dabrafenib plus Trametinib in Stage IIIBRAF -Mutated Melanoma (2017) N. Engl. J. Med., 377 (19), pp. 1813-1823; Hauschild, A., Dummer, R., Schadendorf, D., Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-Mutant stage III melanoma (2018) J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol., p. JCO1801219; Long, G.V., Stroyakovskiy, D., Gogas, H., Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial (2015) Lancet Lond. Engl, 386 (9992), pp. 444-451; Robert, C., Karaszewska, B., Schachter, J., Improved overall survival in melanoma with combined dabrafenib and trametinib (2014) N. Engl. J. Med., 372 (1), pp. 30-39; Schadendorf, D., Hauschild, A., Santinami, M., Effect on health-related quality of life (HRQOL) of adjuvant treatment (tx) with dabrafenib plus trametinib (D + T) in patients (pts) with resected stage III BRAF-mutant melanoma (2018) J. Clin. Oncol., 36 (15_suppl). , 9590–9590; Long, G.V., Flaherty, K.T., Stroyakovskiy, D., 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 (2017) Ann. Oncol. Off. J. Eur. Soc. Med. Oncol, 28 (7), pp. 1631-1639; Robert, C., Karaszewska, B., Schachter, J., Three-year estimate of overall survival in COMBI-v, a randomized phase 3 study evaluating first-line dabrafenib (D) + trametinib (T) in patients (pts) with unresectable or metastatic BRAF V600E/K–mutant cutaneous melanoma (2016) Ann. Oncol.; Verver, D., van Klaveren, D., van Akkooi, A.C.J., Risk stratification of sentinel node–positive melanoma patients defines surgical management and adjuvant therapy treatment considerations (2018) Eur. J. Cancer, 96, pp. 25-33; Balch, C.M., Gershenwald, J.E., Soong, S.-J., Final version of 2009 AJCC melanoma staging and classification (2009) J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol, 27 (36), pp. 6199-6206; Blank, C.U., Rozeman, E.A., Fanchi, L.F., Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (2018) Nat. Med., 24 (11), pp. 1655-1661; Amaria, R.N., Reddy, S.M., Tawbi, H.A., Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma (2018) Nat. Med., 24 (11), pp. 1649-1654; Rozeman, E.A., Menzies, A.M., van Akkooi, A.C.J., 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 (2019) Lancet Oncol., 20 (7), pp. 948-960; Amaria, R.N., Prieto, P.A., Tetzlaff, M.T., 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 (2018) Lancet Oncol., 19 (2), pp. 181-193; Long, G.V., Saw, R.P.M., Lo, S., Neoadjuvant dabrafenib combined with trametinib for resectable, stage IIIB–C, BRAFV600 mutation-positive melanoma (NeoCombi): a single-arm, open-label, single-centre, phase 2 trial (2019) Lancet Oncol., 20 (7), pp. 961-971; Amaria, R.N., Menzies, A.M., Burton, E.M., Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium (2019) Lancet Oncol., 20 (7), pp. e378-e389

PY - 2019

Y1 - 2019

N2 - The past 5 years have witnessed the results of many practice-changing studies that have dramatically improved the landscape of adjuvant therapy in patients with resected, high-risk melanoma. After a 20-year era of adjuvant interferon, the anti-CTLA-4 and anti-PD-1 immune-checkpoint inhibitors, and MAPK-directed targeted therapy brought a revolution into the adjuvant treatment of melanoma. These results came along with the practice-changing results of two large multicenter studies showing no benefit in terms of overall survival for completion lymph node dissection after positive sentinel node biopsy. In this review, we summarized the current state of the art of the adjuvant treatment of high-risk melanoma, with a view on future perspectives. © 2019

AB - The past 5 years have witnessed the results of many practice-changing studies that have dramatically improved the landscape of adjuvant therapy in patients with resected, high-risk melanoma. After a 20-year era of adjuvant interferon, the anti-CTLA-4 and anti-PD-1 immune-checkpoint inhibitors, and MAPK-directed targeted therapy brought a revolution into the adjuvant treatment of melanoma. These results came along with the practice-changing results of two large multicenter studies showing no benefit in terms of overall survival for completion lymph node dissection after positive sentinel node biopsy. In this review, we summarized the current state of the art of the adjuvant treatment of high-risk melanoma, with a view on future perspectives. © 2019

KW - Adjuvant

KW - Immunotherapy

KW - Melanoma

KW - Neoadjuvant

KW - Targeted therapy

KW - alpha interferon

KW - bevacizumab

KW - dabrafenib

KW - ipilimumab

KW - nivolumab

KW - pembrolizumab

KW - trametinib

KW - vemurafenib

KW - adjuvant therapy

KW - cancer staging

KW - colitis

KW - disease classification

KW - distant metastasis free survival

KW - drug efficacy

KW - drug tolerability

KW - fatigue

KW - fever

KW - Guillain Barre syndrome

KW - high risk patient

KW - human

KW - lymph node dissection

KW - lymph node metastasis

KW - melanoma

KW - myocarditis

KW - nausea

KW - overall survival

KW - recurrence free survival

KW - Review

U2 - 10.1016/j.semcancer.2019.08.024

DO - 10.1016/j.semcancer.2019.08.024

M3 - Article

VL - 59

SP - 283

EP - 289

JO - Semin. Cancer Biol.

JF - Semin. Cancer Biol.

SN - 1044-579X

ER -