Systemic therapy of metastatic melanoma.

Abstract

For patients with metastatic melanoma, there are currently several effective therapeutic options. The BRAF inhibitors vemurafenib and dabrafenib are characterized by rapid tumor control and high response rates. In combination with one of the two MEK inhibitors trametinib and cobimetinib, they achieve response rates (CR + PR, complete plus partial remissions) of 70%, while delaying the development of treatment resistance, as well as a median overall survival of > 2 years with tolerable side effects. Showing long-term survival rates of approximately 20%, the anti-CTLA-4 antibody ipilimumab is the first substance that has led to a significant prolongation of overall survival in patients with metastatic melanoma. However, delayed treatment response and severe immune-mediated side effects may pose limitations to its therapeutic benefit. Usually well tolerated, anti-PD-1 antibody monotherapy using nivolumab and pembrolizumab has yielded response rates (CR + PR) of up to 45% and one-year survival rates of > 70%. The combination of ipilimumab and nivolumab has shown response rates of up to 58% and a median progression-free survival of > 11 months. While this combination is expected to result in a rapid and long-lasting response, this potential benefit comes at the expense of a high level of toxicity. Strategies for treatment sequencing and treatment combinations are currently being investigated in clinical studies. Overall, the prognosis for patients with metastatic melanoma has significantly improved. With long-term survival a possibility, not only acute but also long-term therapeutic side effects must be taken into account.

• Authors: Ricarda Rauschenberg, Marlene Garzarolli, Ursula Dietrich, Stefan Beissert, Friedegund Meier
• Journal: Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG (J Dtsch Dermatol Ges) Vol. 13 Issue 12 Pg. 1223-35; quiz 1236-7 (Dec 2015) ISSN: 1610-0387 [Electronic] Germany
• PMID: 26612791 (Publication Type: Journal Article, Review)
• Copyright: © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents

Topics

• Antibodies, Monoclonal (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Evidence-Based Medicine
• Humans
• Melanoma (drug therapy, mortality, secondary)
• Skin Neoplasms (drug therapy, mortality)
• Survival Rate
• Treatment Outcome