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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2024; 84(05): 443-458
DOI: 10.1055/a-2286-6066
GebFra Science
Review/Übersicht

CDK4/6 Inhibition – Therapy Sequences and the Quest to Find the Best Biomarkers – an Overview of Current Programs

Artikel in mehreren Sprachen: English | deutsch
Andreas Schneeweiss
1   National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany
,
Sara Y. Brucker
2   Department of Gynecology and Obstetrics, Tübingen University Hospital, Tübingen, Germany
,
Hanna Huebner
3   Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
,
Lea L. Volmer
2   Department of Gynecology and Obstetrics, Tübingen University Hospital, Tübingen, Germany
,
Carolin C. Hack
3   Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
,
Katharina Seitz
3   Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
,
Matthias Ruebner
3   Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
,
Sabine Heublein
1   National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany
,
Verena Thewes
1   National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany
,
Diana Lüftner
4   Immanuel Hospital Märkische Schweiz & Immanuel Campus Rüdersdorf, Medical University of Brandenburg Theodor-Fontane, Rüdersdorf bei Berlin, Germany
,
Michael P. Lux
5   Department of Gynecology and Obstetrics, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, Germany; St. Vincenz Kliniken Salzkotten + Paderborn, Paderborn, Germany
,
Ingolf Jurhasz-Böss
6   Department of Obstetrics and Gynecology, University Medical Center Freiburg, Freiburg, Germany
,
Florin-Andrei Taran
6   Department of Obstetrics and Gynecology, University Medical Center Freiburg, Freiburg, Germany
,
Pauline Wimberger
7   Department of Gynecology and Obstetrics, Carl Gustav Carus Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany
8   National Center for Tumor Diseases (NCT), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Carl Gustav Carus Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
9   German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
,
Daniel Anetsberger
3   Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
,
Milena Beierlein
3   Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
,
Marcus Schmidt
10   Department of Gynecology and Obstetrics, University Hospital Mainz, Mainz, Germany
,
Julia Radosa
11   Department of Gynecology and Obstetrics, University Hospital Saarland, Homburg, Germany
,
Volkmar Müller
12   Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
,
Wolfgang Janni
13   Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany
,
Brigitte Rack
13   Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany
,
Erik Belleville
14   ClinSol GmbH & Co KG, Würzburg, Germany
,
Michael Untch
15   Clinic for Gynecology and Obstetrics, Breast Cancer Center, Gynecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin, Germany
,
Marc Thill
16   Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt, Germany
,
Nina Ditsch
17   Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany
,
Bahriye Aktas
18   Department of Gynecology, University Hospital Leipzig, Leipzig, Germany
,
Ivonne Nel
18   Department of Gynecology, University Hospital Leipzig, Leipzig, Germany
,
Hans-Christian Kolberg
19   Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany
,
Tobias Engerle
2   Department of Gynecology and Obstetrics, Tübingen University Hospital, Tübingen, Germany
,
Hans Tesch
20   Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany
,
Christian Roos
21   Novartis Pharma GmbH, Nuremberg, Germany
,
Christina Budden
21   Novartis Pharma GmbH, Nuremberg, Germany
,
Hans Neubauer
22   Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany
,
Andreas D. Hartkopf
2   Department of Gynecology and Obstetrics, Tübingen University Hospital, Tübingen, Germany
,
Tanja N. Fehm
22   Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany
23   Centrum für Integrierte Onkologie, Aachen Bonn Köln Düsseldorf, Düsseldorf, Germany
,
Peter A. Fasching
3   Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
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Abstract

In recent years, new targeted therapies have been developed to treat patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer. Some of these therapies have not just become the new therapy standard but also led to significantly longer overall survival rates. The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the therapeutic standard for first-line therapy. Around 70 – 80% of patients are treated with a CDK4/6i. In recent years, a number of biomarkers associated with progression, clonal selection or evolution have been reported for CDK4/6i and their endocrine combination partners. Understanding the mechanisms behind treatment efficacy and resistance is important. A better understanding could contribute to planning the most effective therapeutic sequences and utilizing basic molecular information to overcome endocrine resistance. One study with large numbers of patients which aims to elucidate these mechanisms is the Comprehensive Analysis of sPatial, TempORal and molecular patterns of ribociclib efficacy and resistance in advanced Breast Cancer patients (CAPTOR BC) trial. This overview summarizes the latest clinical research on resistance to endocrine therapies, focusing on CDK4/6 inhibitors and discussing current study concepts.

Keywords

breast cancer - therapy - CDK4/6


Publikationsverlauf

Eingereicht: 25. Dezember 2023

Angenommen nach Revision: 12. März 2024

Artikel online veröffentlicht:
29. Mai 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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