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.
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
