Translationale Highlights Mamma- und Ovarialkarzinom 2019 – Immuntherapien, DNA-Reparatur, PI3K-Inhibition und CDK4/6-Therapien

Zusammenfassung

Im Rahmen von aktuell laufenden Studien werden in naher Zukunft wichtige translationale Fragestellungen von klinischer Relevanz geklärt werden. Zum einen muss die Rolle der PD-L1-Expression, nachdem sie für die Indikationsstellung für Atezolizumab in der 1. Therapielinie bei Patientinnen mit einem metastasierten triple-negativen Mammakarzinom (TNBC) von Relevanz ist, weiter geklärt werden. In einer neoadjuvanten Studie beim TNBC mit Pembrolizumab konnte kein Zusammenhang zwischen Wirksamkeit und PD-L1-Expression gefunden werden. Sowohl mit als auch ohne Expression war die pCR höher, wenn Pembrolizumab zur Chemotherapie hinzugefügt wurde. Des Weiteren wird für die bei Keimbahnmutation von BRCA1/2 zugelassenen PARP-Inhibitoren nach weiteren Patientengruppen gesucht, in denen eine Wirksamkeit besteht. Dieses sind z. B. Patientinnen mit Mutationen in anderen Genen, die an der homologen Rekombination beteiligt sind, oder Patientinnen mit Tumoren, die bei globalen Tests zu homologen Rekombinationsdefizienzen (HRD-Tests) eine Auffälligkeit zeigen. Auch die Frage, ob und mit welchen Chemotherapie-Kombinationspartnern eine PARP-Inhibition zusammen gegeben werden kann, wird aktuell sowohl beim Mamma- als auch beim Ovarialkarzinom untersucht. Während sich die Daten zum verbesserten Gesamtüberleben bei den CDK4/6-Inhibitoren konsolidieren, wächst auch das Wissen um molekulare Veränderungen unter der Therapie und bei der Progression unter der Therapie. Sowohl die Anhäufung von PI3K-Mutationen als auch PTEN-Veränderungen könnten bei der Planung von Folgetherapien eine Rolle spielen. Diese Übersichtsarbeit fasst diese aktuellen Entwicklungen beim Mammakarzinom und teilweise auch beim Ovarialkarzinom zusammen.

Schlüsselwörter

fortgeschrittenes Mammakarzinom - Metastasen - Therapie - Mutationstestung - Immuntherapie - PARP - CDK4/6 - BRCA1/2 - PD-L1

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