Behandlung des metastasierten Melanoms – Update 2025

Fortgeschrittene Melanome weisen eine hohe Metastasierungsrate auf. Durch die modernen Systemtherapien haben sich das progressionsfreie Überleben und das Gesamt-Überleben von Patienten mit metastasiertem Melanom signifikant verbessert – dennoch bleibt die Behandlung eine Herausforderung. Dieser Beitrag beschreibt die aktuelle Therapie des metastasierten Melanoms sowie neue Therapieansätze, die derzeit intensiv untersucht werden.

Abstract

Immune checkpoint inhibition and targeted therapy with BRAF/MEK inhibition for BRAF-mutated melanoma have significantly improved progression-free and overall survival in patients with metastatic melanoma. Current research focuses on novel treatment strategies for PD-1 resistance, neoadjuvant approaches, and cellular therapies. 10-year follow-up data of randomized clinical trials show that both combined CTLA-4 and PD-1 immune checkpoint inhibition and PD-1 immune checkpoint inhibition alone can achieve long-term survival in metastatic melanoma. Potential surrogate markers of long-term response include a progression-free survival at 3 years after start of treatment and a reduction in tumour burden of at least 80%. The management of PD-1 resistance remains a challenge. Advances in molecular pathology have led to the identification of new therapeutic targets. Several cellular therapies are currently being evaluated in clinical trials as alternatives for melanoma patients refractory to immune checkpoint inhibition or targeted BRAF/MEK inhibition. In BRAF-mutant melanoma, combined BRAF/MEK inhibition is an alternative to immune checkpoint inhibition. Real-world data and clinical trial results on treatment sequencing suggest that immune checkpoint inhibition may improve survival in the first line setting, particularly in the absence of prior adjuvant systemic therapy. Adjuvant treatment leads to improved progression-free survival in melanoma patients while overall survival data are still pending. Neoadjuvant treatment seems to be a promising alternative to conventional adjuvant therapy for specific subgroups of melanoma patients. Participation in clinical trials offers patients the best opportunity to benefit from the latest treatment options.

Kernaussagen

• Die Immun-Checkpoint-Inhibition und die zielgerichtete Therapie mit BRAF/MEK-Inhibitoren bei BRAF-Mutation haben zu einem signifikant verbesserten progressionsfreien Überleben und Gesamt-Überleben von Patienten mit metastasiertem Melanom geführt.

• Aktuelle 10-Jahres-Follow-up-Daten zeigen eine langfristige Tumorkontrolle unter einer Immun-Checkpoint-Inhibition. Die Wahl der Immun-Checkpoint-Inhibition sollte individuell mit den Patienten gemeinsam getroffen werden. Mögliche Surrogatmarker für ein exzellentes Langzeit-Ansprechen sind das progressionsfreie Überleben 3 Jahre nach Therapiestart sowie eine Reduktion der Tumorlast von mindestens 80%.

• Die Resistenz auf eine Immun-Checkpoint-Inhibition ist weiterhin eine therapeutische Herausforderung. Dank eines verbesserten molekularpathologischen Verständnisses gibt es zahlreiche neue therapeutische Zielstrukturen. Vielfältige zelluläre Therapieansätze werden aktuell als Therapie-Alternative für Melanom-Patienten, die auf die bisherigen Systemtherapien mit Immun-Checkpoint-Inhibition bzw. zielgerichteter BRAF/MEK-Inhibition therapierefraktär sind, in klinischen Studien getestet.

• Aktuelle Daten aus Real-World-Behandlungsregistern, wie auch Studiendaten zur Sequenztherapie, zeigen eine erhöhte Überlebenswahrscheinlichkeit unter Immun-Checkpoint-Inhibition gegenüber kombinierter BRAF/MEK-Inhibition in der Erstlinien-Therapie, ohne vorherige adjuvante Systemtherapie bei BRAF-mutierten Melanom-Patienten.

• Langzeit-Follow-up-Daten zeigen ein verbessertes progressionsfreies Überleben für die adjuvante Therapie. Jedoch stehen die Auswertungen für das Gesamt-Überleben noch aus. Die neoadjuvante Therapie stellt möglicherweise für Subgruppen von Patienten eine vielversprechende Therapie-Alternative zur konventionellen adjuvanten Therapie dar.

Schlüsselwörter

Immuncheckpoint-Inhibition - zielgerichtete BRAF/MEK-Therapie - personalisierte Therapie - neoadjuvante Therapie

Keywords

immuncheckpoint inhibition - targeted therapy with BRAF/MEK inhibition - personalized therapy - neo-adjvuant therapy

Publication History

Article published online:
22 April 2025

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