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.

Abstract

Despite therapeutic gains in the treatment of HER2-positive (HER2: human epidermal growth factor receptor 2) advanced/metastatic breast cancer, there remains an urgent need for more effective treatment options. At present, there is no definitive approved standard therapy beyond secondline treatment. One of the major challenges is overcoming treatment resistance. Depending on the underlying resistance mechanism, different strategies are being pursued for new innovative treatment concepts in HER2-positive breast cancer. Specifically designed antibodies for targeted therapy are one important focus to successfully meet these challenges. Trastuzumab deruxtecan (T‑DXd, DS-8201a), an optimised antibody drug conjugate (ADC) is in clinical trials, showing promising outcomes in patients with advanced, nonoperable or metastatic HER2-positive breast cancer who had already undergone intensive prior treatment. Based on this data, T‑DXd has already been approved in the US and Japan for HER2-positive advanced nonoperable and metastatic breast cancer – in the US after at least two prior anti-HER2 targeted treatment lines and in Japan after prior chemotherapy. T‑DXd represents successful „antibody engineering“. Since the beginning of the year, T-DXd has also been approved in Europe as monotherapy for inoperable or metastatic HER2-positive breast cancer in patients who are pretreated with at least two anti-HER2 directed therapies. This paper presents strategies for improving treatment options in advanced nonoperable and metastatic HER2-positive breast cancer, with the development of T‑DXd as an example.

Schlüsselwörter

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

Key words

metastatic HER2‑positive breast cancer - HER2‑targeted treatment options - antibody - antibody‑drug conjugate - T‑DXd - DS‑8201

Publication History

Article published online:
30 September 2021

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