Translational Highlights in Breast and Ovarian Cancer 2019 – Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy

Andreas D. Hartkopf; Volkmar Müller; Achim Wöckel; Michael P. Lux; Wolfgang Janni; Johannes Ettl; Erik Belleville; Florian Schütz; Peter A. Fasching; Hans-Christian Kolberg; Manfred Welslau; Friedrich Overkamp; Florin-Andrei Taran; Sara Y. Brucker; Markus Wallwiener; Hans Tesch; Tanja N. Fehm; Andreas Schneeweiss; Diana Lüftner

doi:10.1055/a-1039-4458

Geburtshilfe und Frauenheilkunde, Table of Contents

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2019; 79(12): 1309-1319
DOI: 10.1055/a-1039-4458

GebFra Science

Review/Übersicht

Georg Thieme Verlag KG Stuttgart · New York

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

Article in several languages: English | deutsch

Andreas D. Hartkopf

¹Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany

,

Volkmar Müller

²Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany

,

Achim Wöckel

³Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany

,

Michael P. Lux

⁴Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, Germany

,

Wolfgang Janni

⁵Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Johannes Ettl

⁶Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

,

Erik Belleville

⁷ClinSol GmbH & Co KG, Würzburg, Germany

,

Florian Schütz

⁸Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany

,

Peter A. Fasching

⁹Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Hans-Christian Kolberg

¹⁰Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany

,

Manfred Welslau

¹¹Onkologie Aschaffenburg, Aschaffenburg, Germany

,

Friedrich Overkamp

¹²OncoConsult Hamburg GmbH, Hamburg, Germany

,

Florin-Andrei Taran

¹³Universitätsspital Zürich, Klinik für Gynäkologie, Zürich, Switzerland

,

Sara Y. Brucker

¹Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany

,

Markus Wallwiener

⁸Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany

,

Hans Tesch

¹⁴Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt, Germany

,

Tanja N. Fehm

¹⁵Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany

,

Andreas Schneeweiss

¹⁶National Center for Tumor Diseases, Division Gynecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany

,

Diana Lüftner

¹⁷Charité University Hospital, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumour Immunology, Berlin, Germany

› Author Affiliations

Abstract

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

Full Text

References

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