Abstract
Abstract. Melanoma is the most aggressive skin cancer, and surgery is the standard of care for localised disease. However, a risk of local and distant relapse exists despite tumour removal, particularly with thick or ulcerated tumours or lymph node involvement. Immunotherapy with immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L-1 or CTLA-4 demonstrated improved relapse-free survival and distant metastasis-free survival against placebo after surgery for stage-III and high-risk stage-II melanoma. In unresectable localised and metastatic tumours, the double immunotherapy with ICIs (anti-PD-1+ anti-CTLA-4) allows for long-term survival in more than 50% of the patients. Novel immunotherapies (anti-LAG-3 ICI, adoptive cell therapy, intra-tumoural immunotherapy, cancer vaccines) and new combinations are in development to overcome resistance and improve patients’ survival. Therapeutic decisions for each patient should be discussed in a specialised multidisciplinary team.
Zusammenfassung. Das Melanom ist der aggressivste Hautkrebs, und die chirurgische Entfernung ist die Standardbehandlung für lokalisierte Erkrankungen. Allerdings besteht trotz der Entfernung des Tumors das Risiko eines lokalen Fernrezidivs, insbesondere bei dicken oder ulzerierten Tumoren oder bei Lymphknotenbefall. Die Immuntherapie mit Immuncheckpoint-Inhibitoren, die auf PD-1, PD-L-1 oder CTLA-4 abzielen, hat nach der Operation bei Melanomen im Stadium III und Stadium II mit hohem Risiko im Vergleich zu Placebo eine Verbesserung des rückfallfreien Überlebens und des Überlebens ohne Fernmetastasen belegt. Bei nicht resektablen lokalisierten und metastasierten Tumoren führt die duale Immuntherapie mit Anti-PD-1 und Anti-CTLA-4 bei über 50% der Betroffenen zu einem Langzeitüberleben. Derzeit werden neue Immuntherapien (Anti-LAG-3, adoptive Zelltherapie, intratumorale Immuntherapie, Tumorimpfstoffe) und neue Kombinationen geprüft, um die Tumorresistenz zu bekämpfen und das Überleben zu verbessern. Die Therapieentscheidungen für jede Patientin/jeden Patienten sollten in einem spezialisierten multidisziplinären Team besprochen werden.
Résumé. Le mélanome est le cancer de la peau le plus agressif, et l’exérèse chirurgicale est le traitement standard pour les maladies localisées. Toutefois, il existe un risque de rechute locale et à distance malgré l’ablation de la tumeur, en particulier avec des tumeurs épaisses ou ulcérées ou lors d’une atteinte ganglionnaire. L’immunothérapie avec inhibiteurs du point de contrôle immunitaire ciblant PD-1, PD-L-1 ou CTLA-4 a démontré, après chirurgie, une amélioration de la survie sans rechute et de la survie sans métastases à distance contre le placebo pour les mélanomes de stade III et de stade II à haut risque. Pour les tumeurs localisées et métastatiques non résécables, la double immunothérapie par anti-PD-1 et anti-CTLA-4 permet une survie à long terme chez plus de 50% des patients. De nouvelles immunothérapies (anti-LAG-3, thérapie cellulaire adoptive, immunothérapie intra-tumorale, vaccins anti-tumoral) et de nouvelles combinaisons sont en cours d’évaluation afin de combattre la résistance tumorale et améliorer la survie des patients. Les décisions thérapeutiques pour chaque patient devraient être discutées dans une équipe multidisciplinaire spécialisée.
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