Implementation of CDK4/6 Inhibitors and its Influence on the Treatment Landscape of Advanced Breast Cancer Patients – Data from the Real-World Registry PRAEGNANT

Tobias Engler; Peter A. Fasching; Diana Lüftner; Andreas D. Hartkopf; Volkmar Müller; Hans-Christian Kolberg; Peyman Hadji; Hans Tesch; Lothar Häberle; Johannes Ettl; Markus Wallwiener; Matthias W. Beckmann; Alexander Hein; Erik Belleville; Sabrina Uhrig; Pauline Wimberger; Carsten Hielscher; Christian M. Kurbacher; Rachel Wuerstlein; Michael Untch; Florin-Andrei Taran; Hans-Martin Enzinger; Petra Krabisch; Manfred Welslau; Michael Maasberg; Dirk Hempel; Michael P. Lux; Laura L. Michel; Wolfgang Janni; Diethelm Wallwiener; Sara Y. Brucker; Tanja N. Fehm; Andreas Schneeweiss

doi:10.1055/a-1880-0087

Geburtshilfe und Frauenheilkunde, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2022; 82(10): 1055-1067
DOI: 10.1055/a-1880-0087

GebFra Science

Original Article

Implementation of CDK4/6 Inhibitors and its Influence on the Treatment Landscape of Advanced Breast Cancer Patients – Data from the Real-World Registry PRAEGNANT

Einführung von CDK4/6-Hemmern und deren Auswirkung auf die Behandlungslandschaft bei Patientinnen mit Brustkrebs im fortgeschrittenen Stadium – Real-World-Daten aus dem PRAEGNANT-Register

Tobias Engler

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

,

Peter A. Fasching

²Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

,

Diana Lüftner

³Immanuel Hospital Märkische Schweiz & Medical University of Brandenburg Theodor-Fontane, Brandenburg, Germany

,

Andreas D. Hartkopf

⁴Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Volkmar Müller

⁵Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany

,

Hans-Christian Kolberg

⁶Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany

,

Peyman Hadji

⁷Frankfurt Center for Bone Health, Frankfurt am Main, Germany; Philips-University of Marburg, Marburg, Germany

,

Hans Tesch

⁸Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany

,

Lothar Häberle

²Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

⁹Biostatistics Unit, Department of Gynecology and Obstetrics, Erlangen University Hospital, Erlangen, Germany

,

Johannes Ettl

¹⁰Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

,

Markus Wallwiener

¹¹Department of Obstetrics and Gynecology, Heidelberg University Hospital, Heidelberg, Germany

,

Matthias W. Beckmann

²Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

,

Alexander Hein

²Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

,

Erik Belleville

¹²ClinSol GmbH & Co KG, Würzburg, Germany

,

Sabrina Uhrig

²Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

,

Pauline Wimberger

¹³Department of Gynecology and Obstetrics, Carl Gustav Carus Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany

¹⁴National 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

¹⁵German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany

,

Carsten Hielscher

¹⁶Gynäkologie Kompetenzzentrum – Onkologisches Zentrum Stralsund, Stralsund, Germany

,

Christian M. Kurbacher

¹⁷Department of Gynecology I (Gynecologic Oncology), Gynecologic Center Bonn-Friedensplatz, Bonn, Germany

,

Rachel Wuerstlein

¹⁸Department of Gynecology and Obstetrics, Breast Center and CCC Munich, Munich University Hospital, Munich, Germany

,

Michael Untch

¹⁹Department of Gynecology and Obstetrics, Helios Clinics Berlin-Buch, Berlin, Germany

,

Florin-Andrei Taran

²⁰Department of Obstetrics and Gynecology, Freiburg University Hospital, Freiburg, Germany

,

Hans-Martin Enzinger

²¹Department of Gynecology and Obstetrics, Klinikum Bamberg, Sozialstiftung Bamberg, Bamberg, Germany

,

Petra Krabisch

²²Department of Gynecology and Obstetrics, Klinikum Chemnitz gGmbH, Chemnitz, Germany

,

Manfred Welslau

²³Onkologie Aschaffenburg, Aschaffenburg, Germany

,

Michael Maasberg

²⁴MVZ Hämatologie-Onkologie Mayen/Koblenz GmbH, Mayen, Germany

,

Dirk Hempel

²⁵Onkologiezentrum Donauwörth, Donauwörth, Germany

,

Michael P. Lux

²⁶Department of Gynecology and Obstetrics, Frauenklinik St. Louise, Paderborn, Germany; Frauenklinik St. Josefs-Krankenhaus, Salzkotten, Germany; Kooperatives Brustzentrum Paderborn, St. Vincenz Krankenhaus GmbH, Paderborn, Germany

,

Laura L. Michel

²⁷National Center for Tumor Diseases, Heidelberg University Hospital, German Cancer Research Center (DKFZ), Heidelberg, Germany

,

Wolfgang Janni

⁴Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Diethelm Wallwiener

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

,

Sara Y. Brucker

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

,

Tanja N. Fehm

²⁸Department of Gynecology and Obstetrics, Düsseldorf University Hospital, Düsseldorf, Germany

,

Andreas Schneeweiss

²⁷National Center for Tumor Diseases, Heidelberg University Hospital, German Cancer Research Center (DKFZ), Heidelberg, Germany

› Institutsangaben

Abstract

Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as a standard for the treatment of HER2-negative, hormone receptor-positive (HER2− HR+) breast cancer patients in the first-line advanced therapy setting. Data on patient populations that have been treated in the real-world setting may provide an insight into changes of patient characteristics and prognosis over time.

Methods The data were extracted from the prospective real-world registry PRAEGNANT (NCT02338167). Patients had to have HER2− HR+ advanced breast cancer in the first-line metastatic setting. The chosen therapies were described as well as progression-free survival (PFS) and overall survival (OS) in relation to the given therapies and time periods during which they were indicated.

Results CDK4/6 inhibitors have been rapidly implemented since their introduction in November 2016. In recent years (2018 – 2022), about 70 – 80% of the patient population have been treated with CDK4/6 inhibitors, while endocrine monotherapy was given to about 10% and chemotherapy to about 15% of all patients. The prognosis was worst in patients treated with chemotherapy. Recently, mainly patients with a good prognosis are being treated with endocrine monotherapy, and patients who are treated with chemotherapy have an unfavorable prognosis. The PFS and OS of patients treated with CDK4/6i + ET have remained similar over time despite changes in patient characteristics.

Conclusion A treatment with CDK4/6i + ET has rapidly become the therapy standard for patients in the first-line advanced breast cancer setting. After the implementation of CDK4/6i + ET, endocrine monotherapy is only given to patients with a very favorable prognosis, while chemotherapy is provided to patients with a rather unfavorable prognosis. These changes in patient characteristics did not seem to influence the prognosis of patients treated with CDK4/6i + ET.

Zusammenfassung

Hintergrund Umfangreiche Daten aus prospektiven klinischen Studien liefern einen hohen Evidenzgrad für den Einsatz von CDK4/6-Hemmern in Kombination mit einer endokrinen Therapie (CDK4/6i + ET) als Standard bei der First-Line-Behandlung von metastatischem HER2-negativen hormonrezeptorpositiven (HER2−/HR+) Brustkrebs. Reale Daten von Patientinnengruppen, die damit in der Praxis behandelt wurden, liefern Erkenntnisse über Veränderungen von Patientenmerkmalen und Prognosen im Laufe der Zeit.

Methoden Die Daten wurden dem prospektiven praxisbezogenen PRAEGNANT-Register (NCT02338167) entnommen. Die eingeschlossenen Patientinnen hatten fortgeschrittenen primären und metastasierten HER2−/HR+ Brustkrebs. Die gewählten Therapien, das progressionsfreie Überleben und das Gesamtüberleben der jeweiligen Therapie sowie die Zeitspanne, während der die Behandlung erfolgte, werden dargelegt.

Ergebnisse Nachdem CDK4/6-Hemmer erstmals im November 2016 eingesetzt wurden, stieg die Häufigkeit ihres Einsatzes schnell an. In den letzten Jahren (2018 – 2022) wurden ca. 70 – 80% aller Patientinnengruppen mit CDK4/6-Hemmern behandelt; eine endokrine Monotherapie wurde rund 10% und eine Chemotherapie ungefähr 15% aller Patientinnen verabreicht. Die schlechteste Prognose hatten Patientinnen, die eine Chemotherapie erhielten. Seit Kurzem erhalten hauptsächlich Patientinnen mit guter Prognose eine endokrine Monotherapie; Patientinnen, die eine Chemotherapie erhalten, haben eine ungünstigere Prognose. Das progressionsfreie Überleben und das Gesamtüberleben von mit CDK4/6i + ET behandelten Patientinnen blieb über einen längeren Zeitraum ähnlich, obwohl sich die Patientenmerkmale änderten.

Schlussfolgerung Die Behandlung mit CDK4/6i + ET entwickelte sich rasch zum First-Line-Therapiestandard für Patienten mit fortgeschrittenem Mammakarzinom. Seit der Einführung von CDK4/6i + ET wird die endokrine Monotherapie nur bei Patientinnen mit einer sehr günstigen Prognose eingesetzt, während Chemotherapie meist nur an Patientinnen verabreicht wird, die eine eher ungünstige Prognose haben. Veränderungen der Patientenmerkmale scheinen die Prognose von mit CDK4/6i + ET behandelten Patientinnen nicht zu beeinflussen.

Key words

advanced breast cancer - real world data - chemotherapy - CDK4/6 inhibitor - endocrine treatment

Schlüsselwörter

fortgeschrittenes Mammakarzinom - reale Daten - Chemotherapie - CDK4/6-Hemmer - endokrine Behandlung

Volltext

Referenzen

References
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