TumorDiagnostik & Therapie 2015; 36(03): 146-149
DOI: 10.1055/s-0034-1369665
Schwerpunkt: Melanome
Georg Thieme Verlag KG Stuttgart · New York

Übersicht – Aktuelle Entwicklungen der Systemtherapie des fortgeschrittenen metastasierten Melanoms

M. Schiller
,
J. C. Hassel
Further Information

Publication History

Publication Date:
13 March 2015 (online)

Melanome gehen aus den Melanozyten der Haut und selten auch der Schleimhäute, Uvea oder der Meningen hervor und gehören zu den aggressivsten Tumoren mit drastisch steigender Inzidenz und hoher Therapieresistenz [1]. Neben familiärer Prädisposition, multiplen melanozytären Nävi, einem hellem Hauttyp und einer Immunsuppression werden vor allem Sonnenbrände während der Kindheit, als Zeichen für intermittierend hohe Dosen ultravioletten Lichts, für die Entstehung von Melanomen verantwortlich gemacht. Für das Jahr 2014 prognostizierte das Robert-Koch-Institut für Deutschland rund 19 700 Neuerkrankungen [2]. Die Prognose der Erkrankung richtet sich im Wesentlichen nach der TNM-Klassifikation und dem daraus resultierenden Stadium des American Joint Committee on Cancer (AJCC) 2009, wobei die Chance für eine kurative Therapie in den frühen Tumorstadien am größten ist [3]. Doch durch neue Therapieansätze haben sich die Chancen einer langfristigen Kontrolle auch beim fernmetastasierten Melanom erhöht.

 
  • Literatur

  • 1 Lo JA, Fisher DE. The melanoma revolution: from UV carcinogenesis to a new era in therapeutics. Science, 2014 346: 945–949.
  • 2 Robert Koch-Institut (Hrsg.) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V.. Krebs in Deutschland 2009/2010. 9. 2013
  • 3 Balch CM et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol, 2009; 27: 6199-6206
  • 4 Eggermont AM, Kirkwood JM. Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?. Eur J Cancer 2004; 40: 1825-1836
  • 5 Davies H et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949-954
  • 6 Pflugfelder A et al. , et al. Malignant melanoma S3-guideline „diagnosis, therapy and follow-up of melanoma“. J Dtsch Dermatol Ges 2013; 11 (Suppl. 06) 1-126
  • 7 Chapman PB et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-2516
  • 8 Hauschild A et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380: 358-365
  • 9 Hauschild A et al. An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM). J Clin Oncol ASCO Annual Meeting Abstracts 2013; 31 (Suppl. 15)
  • 10 McArthur GA 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
  • 11 Sosman JA et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012; 366: 707-714
  • 12 Larkin J et al. Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol 2014; 15: 436-444
  • 13 Long GV et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 1087-1095
  • 14 Anker CJ et al. Severe liver and skin toxicity after radiation and vemurafenib in metastatic melanoma. J Clin Oncol 2013; 31: e283-287
  • 15 Conen K et al. Vemurafenib-Induced Radiation Recall Dermatitis: Case Report and Review of the Literature. Dermatology 2015; 230: 1-4
  • 16 Houriet C et al. Localized Epidermal Cysts as a Radiation Recall Phenomenon in a Melanoma Patient Treated with Radiotherapy and the BRAF Inhibitor Vemurafenib. Case Rep Dermatol 2014; 6: 213-217
  • 17 Lang N et al. Cutis verticis gyrata-like skin toxicity during treatment of melanoma patients with the BRAF inhibitor vemurafenib after whole-brain radiotherapy is a consequence of the development of multiple follicular cysts and milia. Strahlenther Onkol 2014; 190: 1080-1081
  • 18 Rompoti N et al. Combination of BRAF Inhibitors and Brain Radiotherapy in Patients With Metastatic Melanoma Shows Minimal Acute Toxicity. J Clin Oncol 2013; 31: 3844-3845
  • 19 Schulze B et al. Unusual acute and delayed skin reactions during and after whole-brain radiotherapy in combination with the BRAF inhibitor vemurafenib. Two case reports. Strahlenther Onkol 2014; 190: 229-232
  • 20 Van Allen EM et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014; 4: 94-109
  • 21 Flaherty KT et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 2012; 367: 1694-1703
  • 22 Long GV et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014; 371: 1877-1888
  • 23 Robert C et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015; 372: 30-39
  • 24 Larkin J et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014; 371: 1867-1876
  • 25 Fedorenko IV et al. Beyond BRAF: where next for melanoma therapy?. Br J Cancer 2015; 112: 217-226
  • 26 Guo J et al. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol 2011; 29: 2904-2909
  • 27 Carvajal RD et al. KIT as a therapeutic target in metastatic melanoma. JAMA 2011; 305: 2327-2334
  • 28 Hodi FS et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723
  • 29 Lebbe C et al. Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies. Ann Oncol 2014; 25: 2277-2284
  • 30 Dick J et al. Long-Lasting Responses under Treatment with Ipilimumab: An Argument against Maintenance Therapy?. Dermatology 2015; 230: 8-10
  • 31 Robert C et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. N Engl J Med 2015; 372: 320-330
  • 32 Robert C et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384: 1109-1117
  • 33 Wolchok JD et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15: 7412-7420
  • 34 Berthod G et al. Pulmonary sarcoid-like granulomatosis induced by ipilimumab. J Clin Oncol 2012; 30: e156-159
  • 35 Eckert A et al. Anti-CTLA4 monoclonal antibody induced sarcoidosis in a metastatic melanoma patient. Dermatology 2009; 218: 69-70
  • 36 Murphy KP et al. New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment. Oncol Res Treat 2014; 37: 351-353
  • 37 Reule RB, North JP. Cutaneous and pulmonary sarcoidosis-like reaction associated with ipilimumab. J Am Acad Dermatol 2013; 69: e272-273
  • 38 Tissot C et al. Sarcoidosis complicating anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody biotherapy. Eur Respir J 2013; 41: 246-247
  • 39 Vogel WV et al. Ipilimumab-induced sarcoidosis in a patient with metastatic melanoma undergoing complete remission. J Clin Oncol 2012; 30: e7-e10
  • 40 Luke JJ, Hodi FS. Ipilimumab, vemurafenib, dabrafenib, and trametinib: synergistic competitors in the clinical management of BRAF mutant malignant melanoma. Oncologist 2013; 18: 717-725
  • 41 Ackerman A et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer 2014; 120: 1695-1701
  • 42 Hu-Lieskovan S et al. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol 2014; 32: 2248-2254
  • 43 Ribas A et al. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med 2013; 368: 1365-1366