Aktuelle Systemtherapie des metastasierten malignen Melanoms – Zielgerichtete Therapien und Immuntherapie als vielversprechende Optionen

Noch bis vor wenigen Jahren galt das metastasierte Melanom als therapierefraktärer Tumor. Die aktuellen Zulassungen der Kombination aus BRAF- und MEK-Inhibitoren sowie der PD-1-Checkpointinhibitoren erweitern das therapeutische Portfolio der Dermatoonkologie für Patienten mit fortgeschrittenem Melanom deutlich. Für die Kombinationstherapien aus BRAF- und MEK-Inhibitoren werden mittlerweile objektive Ansprechraten von bis zu 70 % mit einem medianen Überleben von rund 28 Monaten angegeben. Durch die Therapie mit CTLA-4-Inhibitoren scheinen zudem rund 20 % der Patienten ein Langzeitüberleben zu erreichen. Mit der Verfügbarkeit der PD-1-Inhibitoren erhofft man sich, diesen Anteil der Patienten noch erhöhen zu können. Aktuell liegt das 2-Jahres-Überleben bei rund 40 %. In Zukunft müssen klinische Studien klären, in welcher Sequenz, Kombination und Dauer die einzelnen Substanzen zum Einsatz kommen müssen, um das entscheidende Ziel für den Patienten zu erreichen: Eine Heilung oder zumindest der Übergang in eine langfristige, kontrollierte Erkrankung.

Only a few years ago metastatic melanoma was considered as a refractory disease. The latest approvals of the combined therapy of BRAF and MEK inhibitors, as well as the approvals of PD-1 checkpoint inhibitors enhance the therapeutic portfolio in dermatooncology for patients suffering from advanced melanoma significantly. With the combination of BRAF- and MEK-Inhibitors objective response rates of up to 70% can be achieved with a median survival of about 28 months. Moreover, due to the treatment with CTLA-4 inhibitors about 20% of patients appear to achieve a long term survival. PD-1 inhibitors are believed to be able to increase this proportion of patients. Right now, the 2-Year overall survival rate reaches approximately 40%. In the future, clinical trials need to clarify in what sequence, combination and duration of the individual substances must be used in order to achieve the ultimate goal for the patient: cure or at least the transition to a long-term, controlled disease.

Key words

Advanced melanoma - BRAF-inhibitors - MEK-inhibitors - Checkpoint-inhibitors

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