memo - Magazine of European Medical Oncology

, Volume 6, Issue 4, pp 244–246

ASCO 2013—treatment of metastatic melanoma: is it still a story of success?

short review


‘There is a light at the end of the tunnel in the treatment of metastatic melanoma’ was the slogan of enthusiastic dermatologists around the world in 2010, when two new substances were approved by the Food and Drug Association in the United States and later on, the European Medicines Agency in Europe. Ipilimumab (Yervoy®) is a fully human monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4, which switches off the mechanism of immune suppression and enables continuous, unrestrained stimulation of T-cells by dendritic cells. The objective response rates are only 10–15 %, but most of them are long lasting. The second approved substance is vemurafenib (Zelboraf®), a selective BRAF inhibitor. BRAF is a member of the Raf family, which is part of the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signalling pathway. Approximately 40–60 % of cutaneous melanomas carry mutations in BRAF that lead to constitutive activation of downstream signalling through the MAPK pathway. However, the duration of response has been limited, as resistance to BRAF inhibitors develops within months after initiation of treatment. So in 2013 the question arises, whether the story of success in the treatment of metastatic melanoma is prolonged and whether there are some new promising substances in the treatment pipeline. At American Society of Clinical Oncology 2013, actual data of studies with other immune checkpoint molecules, such as programmed death-1 antibodies or antibodies against its ligand programmed death ligand 1, were presented, as well as data from downstream molecules of the MAPK pathway (e.g. MEK inhibitors). The most promising response rates, however, can be observed by combining these new substances.


Melanoma CTLA-4 PD-1 BRAF MEK 


  1. 1.
    Hodi FS, Lee SJ, McDermott DF, et al. Multicenter, randomized phase II trial of GM-CSF (GM) plus ipilimumab (Ipi) versus Ipi alone in metastatic melanoma: E1608. J Clin Oncol. 2013;31 (Suppl; abstr CRA9007).Google Scholar
  2. 2.
    Sznol M, Kluger HM, Hodi FS, et al. Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538). J Clin Oncol. 2013;31 (Suppl; abstr CRA9006^).Google Scholar
  3. 3.
    Ribas A, Robert C, Daud A, et al. Clinical efficacy and safety of lambrolizumab (MK-3475, Anti-PD-1 monoclonal antibody) in patients with advanced melanoma. J Clin Oncol. 2013;31 (Suppl; abstr 9009).Google Scholar
  4. 4.
    Hamid O, Robert C, Daud A, Hodi FS, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134–44.PubMedCrossRefGoogle Scholar
  5. 5.
    Wolchok JD, Kluger HM, Callahan MK, et al. Safety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL). J Clin Oncol 2013;31 (Suppl; abstr 9012^).Google Scholar
  6. 6.
    Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jul 11;369(2):122–33.PubMedCrossRefGoogle Scholar
  7. 7.
    Hauschild A, Grob JJ, Demidov LV, 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. 2013; (Suppl; abstr 9013).Google Scholar
  8. 8.
    Harding JJ, Catalanotti F, Yaqubie A, et al. Vemurafenib (VEM) in patients (pts) with BRAF-mutant melanoma and brain metastases (mets). J Clin Oncol. 2013;31 (Suppl; abstr 9060).Google Scholar
  9. 9.
    Dzienis MR, Atkinson V. Response rate to vemurafenib in BRAF-positive melanoma brain metastases. J Clin Oncol. 2013;31 (Suppl; abstr 9081).Google Scholar
  10. 10.
    Long GV, Trefzer U, Davies MA, 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 Nov;13(11):1087–95.PubMedCrossRefGoogle Scholar
  11. 11.
    Sosman JA, Daud A, Weber JS, et al. BRAF inhibitor (BRAFi) dabrafenib in combination with the MEK1/2 inhibitor (MEKi) trametinib in BRAFi-naive and BRAFi-resistant patients (pts) with BRAF mutation-positive metastatic melanoma (MM). J Clin Oncol 2013;31 (Suppl; abstr 9005).Google Scholar
  12. 12.
    Kefford R, Miller WH, Shao-Weng Tan D, et al. Preliminary results from a phase Ib/II, open-label, dose-escalation study of the oral BRAF inhibitor LGX818 in combination with the oral MEK1/2 inhibitor MEK162 in BRAF V600-dependent advanced solid tumors. J Clin Oncol. 2013;31 (Suppl; abstr 9029).Google Scholar
  13. 13.
    Ribas A, Hodi FS, Callahan M, et al. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med. 2013 Apr 4;368(14):1365–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Ascierto PA, Simeone E, Chiarion-Sileni V, et al. Sequential treatment with ipilimumab and BRAF inhibitors in patients with metastatic melanoma: data from the Italian cohort of ipilimumab expanded access programme (EAP). J Clin Oncol. 2013;31, (suppl; abstr 9035).Google Scholar
  15. 15.
    Hodi FS, Amin A, Saenger YM, et al. CA184–240: a single-arm, open-label phase II study of vemurafenib followed by ipilimumab in patients with BRAF V600-mutated advanced melanoma (AM). J Clin Oncol. 2013;31 (suppl; abstr TPS9103).Google Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Clinical Department of Dermatology and VenerologyMedical University InnsbruckInnsbruckAustria

Personalised recommendations