Neue Therapiestrategien beim HER2-positiven fortgeschrittenen, inoperablen bzw. metastasierten Mammakarzinom

Zusammenfassung

Trotz therapeutischer Fortschritte bei der Behandlung des HER2-positiven (HER2: humaner epidermaler Wachstumsfaktor-Rezeptor 2) fortgeschrittenen/metastasierten Mammakarzinoms besteht weiterhin ein dringender Bedarf an wirksameren Therapieoptionen. Jenseits der zweiten Therapielinie gibt es derzeit keinen definierten, zugelassenen Therapiestandard. Eine der großen Herausforderungen ist die Überwindung von Therapieresistenzen. In Abhängigkeit vom zugrunde liegenden Resistenzmechanismus werden verschiedene Strategien für neue innovative Therapiekonzepte beim HER2-positiven Mammakarzinom verfolgt. Ein wichtiger Fokus liegt dabei auf spezifisch designten Antikörpern für eine gezielte Therapie, um diesen Herausforderungen erfolgreich zu begegnen. Mit Trastuzumab-Deruxtecan (T-DXd, DS-8201a) befindet sich ein optimiertes Antikörper-Wirkstoff-Konjugat (ADC: Antibody Drug Conjugate) in der klinischen Prüfung, das vielversprechende Studienergebnisse bei bereits intensiv vorbehandelten Patienten mit fortgeschrittenem, inoperablem oder metastasiertem, HER2-positivem Mammakarzinom zeigt. Aufgrund dieser Datenlage ist T-DXd in den USA und Japan bereits für das HER2-positive fortgeschrittene, inoperable bzw. metastasierte Mammakarzinom zugelassen – in den USA nach mindestens 2 vorangegangenen anti-HER2 zielgerichteten Therapielinien und in Japan nach vorangegangener Chemotherapie. T-DXd steht stellvertretend für ein erfolgreiches „Antikörper-Engineering“. Seit Anfang des Jahres ist T-DXd auch in Europa als Monotherapie beim inoperablen oder metastasierten HER2-positiven Mammakarzinom zugelassen bei Patienten, die mindestens 2 gegen HER2 gerichtete Vorbehandlungen erhalten haben. In der vorliegenden Publikation werden Strategien zur Verbesserung von Therapieoptionen beim HER2-positiven fortgeschrittenen, inoperablen bzw. metastasierten Mammakarzinom vorgestellt – unter anderem am Beispiel der Entwicklung von T-DXd.

Schlüsselwörter

metastasiertes HER2-positives Mammakarzinom - HER2-gerichtete Therapieoptionen - Antikörper - Antikörper-Wirkstoff-Konjugat - T-DXd - DS-8201

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