Historisch gezien werd adjuvante therapie bij het melanoom wereldwijd niet veel toegepast, omdat er weinig tot geen effectieve systemische therapie-opties beschikbaar waren. Interferon (IFN) is uitgebreid bestudeerd in verschillende schema’s (hoge, intermediaire, lage dosis, pegylated-IFN, met of zonder inductiefase, kortere en langere onderhoudsdosering), maar in algemene zin was het effect minimaal.1-10 Een meta-analyse van de grootste adjuvante EORTC-trials en een ‘individual patient data’ meta-analyse van 15 adjuvante trials toonde gemiddeld genomen wel enig voordelig effect op recidiefvrije overleving, maar weinig tot geen effect op melanoomspecifieke of algehele overleving, behalve voor patiënten met een geulcereerd primair melanoom.1
Bronnen:
- Ives NJ, Suciu S, Eggermont AMM, et al., on behalf of the International Melanoma Meta-Analysis Collaborative Group (IMMCG). Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis. Eur J Cancer. 2017;82:171-183,Robert C, Karaszewska B, Schachter J, et al: Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 372:30-9, 2015,Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan 22;372(4):320-30.,Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017 Oct 5;377(14):1345-1356.,Long GV, Atkinson V, Cebon JS, et al. Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (KEYNOTE-029): an open-label, phase 1b trial. Lancet Oncol. 2017 Sep;18(9):1202-1210.,van der Ploeg AP, van Akkooi AC, Haydu LE, et al: The prognostic significance of sentinel node tumour burden in melanoma patients: an international, multicenter study of 1539 sentinel node-positive melanoma patients. Eur J Cancer 50:111-20, 2014,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 16:522-30, 2015,Eggermont AM, Chiarion-Sileni V, Grob JJ, et al: Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med 375:1845-1855, 2016,Tarhini AA, Lee SJ, Hodi FS, et al. 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. J Clin Oncol 2019;(Suppl): Abstract 9504,Weber J, Mandala M, Del Vecchio M, et al: Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med 377:1824-1835, 2017,Eggermont AMM, Blank CU, Mandala M, et al: Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med 378:1789-1801, 2018,Lewis K, Maio M, Demidov LV, et al: BRIM8: a randomized, double-blind, placebo-controlled study of adjuvant vemurafenib in patients (pts) with completely resected, BRAF V600+ melanoma at high risk for recurrence. Ann Oncol:LBA7_PR, 2017,Long GV, Hauschild A, Santinami M, et al: Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med 377:1813-1823, 2017,Amaria RN, Pieto PA, Tetzlaff MT,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 Feb;19(2):181-193. ,Amaria RN, Reddy SM, Tawbi HA, et al: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med 24:1649-1654, 2018,Blank CU, Rozeman EA, Fanchi LF, et al: Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med 24:1655-1661, 2018,Rozeman EA, Menzies AM, van der Wiel B, et al: OpACIN-neo – A Multicenter Phase 2 Study to identify the Optimal neo-Adjuvant Combination scheme of Ipilimumab (IPI) and Nivolumab (NIVO). Ann Oncol:LBA42, 2018