TumorDiagnostik & Therapie 2018; 39(02): 105-109
DOI: 10.1055/s-0044-100836
Schwerpunkt Melanome
© Georg Thieme Verlag KG Stuttgart · New York

Systemtherapie des fortgeschrittenen metastasierten Melanoms

Johannes Kleemann
,
Markus Meissner
Further Information

Publication History

Publication Date:
02 March 2018 (online)

Für die Therapie des fortgeschrittenen malignen Melanoms wurden in den letzten Jahren zahlreiche neue Substanzen zugelassen, die erstmalig das Gesamtüberleben von Patienten positiv beeinflussen können. Dieser Beitrag fasst den aktuellen klinischen Stand der modernen Melanomtherapie zusammen und gibt einen Ausblick auf Entwicklungen in der adjuvanten Therapie.

 
  • Literatur

  • 2 Hodi FS, O’Day SJ, McDermott DF. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723
  • 3 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: 1191-1196
  • 4 Hodi FS. Cytotoxic T-lymphocyte-associated antigen-4. Clin Cancer Res 2007; 13: 5238-5242
  • 5 Merelli B, Massi D, Cattaneo L. et al. Targeting the PD1/PD-L1 axis in melanoma: biological rationale, clinical challenges and opportunities. Crit Rev Oncol Hematol 2014; 89: 140-165
  • 6 Obeid JM, Erdag G, Smolkin ME. et al. PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: Correlation with tumor-infiltrating immune cells and clinical outcome. Oncoimmunol 2016; 5: e1235107
  • 7 Robert C, Long GV, Brady B. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372: 320-330
  • 8 Hodi FS, Kluger H, Sznol M. et al. Abstract CT001: Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial. Cancer Res 2016 76. Abstr. CT001
  • 9 Robert C, Schachter J, Long GV. et al. Pembrolizumab vs. Ipilimumab in Advanced Melanoma. N Engl J Med 2015; 372: 2521-2532
  • 10 Schachter J, Ribas A, Long GV. et al. Pembrolizumab vs. ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet 2017; 390: 1853-1862
  • 11 Robert C, Ribas A, Hamid O. et al. Three-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. J Clin Oncol 2016; 34: 9503-9503
  • 12 Larkin J, Chiarion-Sileni V, Gonzalez R. et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015; 373: 23-34
  • 13 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: 1345-1356
  • 14 Tawbi H, Forsyth P, Algazi A. et al. Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204. J Clin Oncol 2017; 35: 9507-9507
  • 15 Kahler KC, Hauschild A. Treatment and side effect management of CTLA-4 antibody therapy in metastatic melanoma. J Dtsch Dermatol Ges 2011; 9: 277-286
  • 16 Davies H, Bignell GR, Cox C. et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949-954
  • 17 Cancer Genome Atlas N. Genomic Classification of Cutaneous Melanoma. Cell 2015; 161: 1681-1696
  • 18 Chapman PB, Hauschild A, Robert C. et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-2516
  • 19 McArthur GA, Chapman PB, Robert C. et al. 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. Lancet Oncol 2014; 15: 323-332
  • 20 Hauschild A, Grob JJ, Demidov LV. et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380: 358-365
  • 21 Hauschild A, Grobb J, Demidov L. et al. 1092PD An Update on Overall Survival (Os) and Follow-on Therapies in Break-3, a Phase Iii, Randomized Trial: Dabrafenib (D) Vs. Dacarbazine (Dtic) in Patients (Pts) with Braf V600e Mutation-Positive Metastatic Melanoma (Mm). Ann Oncol 2014; 25: iv378-iv378
  • 22 Gibney GT, Messina JL, Fedorenko IV. et al. Paradoxical oncogenesis – the long-term effects of BRAF inhibition in melanoma. Nat Rev Clin Oncol 2013; 10: 390-399
  • 23 Spagnolo F, Ghiorzo P, Queirolo P. Overcoming resistance to BRAF inhibition in BRAF-mutated metastatic melanoma. Oncotarget 2014; 5: 10206-10221
  • 24 Ascierto PA, McArthur GA, Dréno B. et al. Cobimetinib combined with vemurafenib in advanced BRAF V600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016; 17: 1248-1260
  • 25 Long GV, Flaherty KT, Stroyakovskiy D. et al. Dabrafenib plus trametinib vs. dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol 2017; 28: 1631-1639
  • 26 Davies MA, Saiag P, Robert C. et al. Dabrafenib plus trametinib in patients with BRAF V600 -mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol 2017; 18: 863-873
  • 27 Harrington KJ, Puzanov I, Hecht JR. et al. Clinical development of talimogene laherparepvec (T-VEC): a modified herpes simplex virus type-1-derived oncolytic immunotherapy. Expert Rev Anticancer Ther 2015; 15: 1389-1403
  • 28 Liu BL, Robinson M, Han ZQ. et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 2003; 10: 292-303
  • 29 Andtbacka RH, Kaufman HL, Collichio F. et al. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol 2015; 33: 2780-2788
  • 30 Harrington KJ, Andtbacka RH, Collichio F. et al. Efficacy and safety of talimogene laherparepvec vs. granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial. Onco Targets Ther 2016; 9: 7081-7093
  • 31 Chesney J, Puzanov I, Collichio F. et al. Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Vs. Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma. J Clin Oncol 2017; DOI: 10.1200/JCO.2017.73.7379: JCO2017737379.
  • 32 Long GV, Dummer R, Ribas A. et al. A Phase I/III, multicenter, open-label trial of talimogene laherparepvec (T-VEC) in combination with pembrolizumab for the treatment of unresected, stage IIIb-IV melanoma (MASTERKEY-265). J Immun Therap Cancer 2015; 3: P181
  • 33 Ribas A, Dummer R, Puzanov I. et al. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell 2017; 170: 1109-1119
  • 34 Ives NJ, 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: 171-183
  • 35 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: 1845-1855
  • 36 Weber J, Mandala M, Del Vecchio M. et al. Adjuvant Nivolumab vs. Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med 2017; 377: 1824-1835
  • 37 Long GV, Hauschild A, Santinami M. et al. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med 2017; 377: 1813-1823