Management of Localized Melanoma in the Anti-PD-1 Era

doi:10.1007/s11912-024-01556-z

Review

. 2024 Jun 6.

doi: 10.1007/s11912-024-01556-z. Online ahead of print.

Management of Localized Melanoma in the Anti-PD-1 Era

Elan Novis^{1

2}, Alexander C J van Akkooi^{3

4

5}

Affiliations

¹ Melanoma Institute Australia, 40 Rocklands Road, Wollstonecraft, North Sydney, Sydney, NSW, 2060, Australia.
² Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
³ Melanoma Institute Australia, 40 Rocklands Road, Wollstonecraft, North Sydney, Sydney, NSW, 2060, Australia. alexander.vanakkooi@melanoma.org.au.
⁴ Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. alexander.vanakkooi@melanoma.org.au.
⁵ Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. alexander.vanakkooi@melanoma.org.au.

PMID: 38842606
DOI: 10.1007/s11912-024-01556-z

Review

Management of Localized Melanoma in the Anti-PD-1 Era

Elan Novis et al. Curr Oncol Rep. 2024.

. 2024 Jun 6.

doi: 10.1007/s11912-024-01556-z. Online ahead of print.

Authors

Elan Novis^{1

2}, Alexander C J van Akkooi^{3

4

5}

Affiliations

¹ Melanoma Institute Australia, 40 Rocklands Road, Wollstonecraft, North Sydney, Sydney, NSW, 2060, Australia.
² Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
³ Melanoma Institute Australia, 40 Rocklands Road, Wollstonecraft, North Sydney, Sydney, NSW, 2060, Australia. alexander.vanakkooi@melanoma.org.au.
⁴ Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. alexander.vanakkooi@melanoma.org.au.
⁵ Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. alexander.vanakkooi@melanoma.org.au.

PMID: 38842606
DOI: 10.1007/s11912-024-01556-z

Abstract

Purpose of review: The management of cutaneous melanoma has rapidly progressed over the past decade following the introduction of effective systemic therapies. Given the large number of recent clinical trials which have dramatically altered the management of these patients, an updated review of the current evidence regarding the management of localized melanoma is needed.

Recent findings: The role of effective systemic therapies in earlier stages (I-III) melanoma, both in adjuvant and neoadjuvant settings is rapidly changing the role of surgery in the management cutaneous melanoma, particularly regarding surgical safety margins for wide local excision (WLE), the role of sentinel lymph node biopsy (SLNB) and the extent of lymph node dissections. The randomized phase 2 SWOG1801 trial has demonstrated superiority of neoadjuvant-adjuvant anti-PD1 therapy in improving event-free survival by 23% at 2-years over adjuvant anti-PD-1 therapy only. Furthermore, the PRADO trial has suggested a more tailored approach both the extent of surgery as well as adjuvant therapy can safely and effectively be done, depending on the response to initial neoadjuvant immunotherapy. These results await validation and it is expected that in 2024 the phase 3 Nadina trial (NCT04949113) will definitively establish neo-adjuvant combination immunotherapy as the novel standard. This will further redefine the management of localized melanoma. The use of effective systemic therapies will continue to evolve in the next decade and, together with new emerging diagnostic and surveillance techniques, will likely reduce the extent of routine surgery for stage I-III melanoma.

Keywords: Adjuvant; Cutaneous melanoma; Immunotherapy; Lymph Node; Neoadjuvant; Sentinel Node; Targeted therapy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

1. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. https://doi.org/10.1056/NEJMoa1003466 . - DOI - PubMed - PMC
1. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. https://doi.org/10.1056/NEJMoa1103782 . - DOI - PubMed - PMC
1. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, ChiarionSileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Casey M, Ouellet D, Martin AM, Le N, Patel K, Flaherty K. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877–88. https://doi.org/10.1056/NEJMoa1406037 . - DOI - PubMed
1. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521–32. https://doi.org/10.1056/NEJMoa1503093 . - DOI - PubMed
1. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30. https://doi.org/10.1056/NEJMoa1412082 . - DOI - PubMed

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[1] Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. https://doi.org/10.1056/NEJMoa1003466 . - DOI - PubMed - PMC

[2] Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. https://doi.org/10.1056/NEJMoa1003466 . - DOI - PubMed - PMC

[3] Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. https://doi.org/10.1056/NEJMoa1103782 . - DOI - PubMed - PMC

[4] Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. https://doi.org/10.1056/NEJMoa1103782 . - DOI - PubMed - PMC

[5] Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, ChiarionSileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Casey M, Ouellet D, Martin AM, Le N, Patel K, Flaherty K. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877–88. https://doi.org/10.1056/NEJMoa1406037 . - DOI - PubMed

[6] Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, ChiarionSileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Casey M, Ouellet D, Martin AM, Le N, Patel K, Flaherty K. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877–88. https://doi.org/10.1056/NEJMoa1406037 . - DOI - PubMed

[7] Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521–32. https://doi.org/10.1056/NEJMoa1503093 . - DOI - PubMed

[8] Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521–32. https://doi.org/10.1056/NEJMoa1503093 . - DOI - PubMed

[9] Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30. https://doi.org/10.1056/NEJMoa1412082 . - DOI - PubMed

[10] Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30. https://doi.org/10.1056/NEJMoa1412082 . - DOI - PubMed

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Management of Localized Melanoma in the Anti-PD-1 Era

Affiliations

Management of Localized Melanoma in the Anti-PD-1 Era

Authors

Affiliations

Abstract

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Abstract

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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