Endlich neue Therapieoptionen beim malignen Melanom

Zusammenfassung

Die Therapie des malignen Melanoms hat sich in den letzten Jahren grundlegend verändert. Als neue Therapieoptionen stehen nun zielgerichtete Hemmstoffe bei Vorliegen von BRAFV600-Mutationen sowie Ipilimumab als Immuntherapie zur Verfügung. BRAF-Mutationen liegen bei etwa 50 % der Patienten vor. Die BRAF-Inhibitoren Vemurafenib und Dabrafenib zeigen objektive Ansprechraten von rund 60 % sowie ein rasches Ansprechen bei relativ guter Verträglichkeit, haben allerdings eine auf durchschnittlich 7 Monate begrenzte Ansprechdauer. Die Immuntherapie mit Ipilimumab hat zwar deutlich geringere Ansprechraten und kann schwere immunvermittelte Nebenwirkungen hervorrufen, das Ansprechen kann aber jahrelang anhalten. In klinischen Studien werden MEK-Inhibitoren bei Vorliegen von NRAS-Mutationen sowie in der Kombination mit BRAF-Inhibitoren bei BRAF-mutierten Melanomen zur Verzögerung der Resistenzentwicklung getestet. Als Immuntherapien werden PD1-Antikörper allein oder in Kombination mit Ipilimumab getestet. Die Kombination zeigt die bislang vielversprechendsten Ergebnisse mit Ansprechraten von über 50 %, Tumorreduktionen von über 80 % und längerfristiger Ansprechdauer bei allerdings erhöhter Toxizität. Die neuen Optionen haben die Prognose und die Therapie des fortgeschrittenen Melanoms entscheidend verbessert. Unter Berücksichtigung verschiedener Faktoren wie die Lebenserwartung und das Mutationsprofil ist es die herausfordernde Aufgabe des behandelnden Arztes, die optimale Therapieoption auszuwählen.

Abstract

In recent years there has been a fundamental change in the treatment of melanoma. New therapeutic options such as the targeted therapy of BRAF-mutated melanoma and the immunotherapy ipilimumab are available. In about 50 % of melanoma patients a BRAF mutation is found. BRAF inhibitors dabrafenib and vemurafenib show objective response rates of about 60 % with quick responses and relatively good tolerability. However, duration of the response is usually limited to a median of 7 months. Immunotherapy with ipilimumab has significantly lower response rates and may cause severe immune-related adverse events, but the response may last for years. MEK inhibitors in NRAS-mutated melanoma and in combination with BRAF inhibitors in BRAF-mutated melanoma to delay development of resistance are being investigated in clinical studies. Immunotherapy with PD-1 antibodies is being tested as monotherapy or in combination with ipilimumab. This combination has shown most promising results with response rates of over 50 %, a tumor reduction of 80 % and durable responses albeit increased toxicities.

These new therapeutic options have significantly improved the prognosis and therapy of advanced melanoma. Taking into account life expectancy and tumor mutation profile it is the challenging task of the treating physician to choose the optimal therapy.

Schlüsselwörter

BRAF - malignes Melanom - zielgerichtete Therapie - Immuntherapien - Ipilimumab

Keywords

BRAF - malignant melanoma - targeted therapies - immunotherapies - ipilimumab

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