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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2024; 84(05): 459-469
DOI: 10.1055/a-2286-5372
GebFra Science
Original Article

Attrition in the First Three Therapy Lines in Patients with Advanced Breast Cancer in the German Real-World PRAEGNANT Registry

Real-World-Daten des deutschen PRAEGNANT-Registers zu Therapieabbrüchen der ersten 3 Therapielinien bei Patientinnen mit fortgeschrittenem Brustkrebs
Andreas D. Hartkopf‡
19   Breast Center and CCC Munich, Dept of Gynecology and Obstetrics, University Hospital LMU Munich, Munich, Germany
,
Christina B. Walter‡
1   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
,
Hans-Christian Kolberg
2   Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany
,
Peyman Hadji
3   Frankfurt Center for Bone Health, Frankfurt am Main, Germany
,
Hans Tesch
4   Oncology Practice, Bethanien Hospital, Frankfurt am Main, Germany
,
Peter A. Fasching
5   Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Germany
,
Johannes Ettl
6   Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
7   Cancer Center Kempten/Allgäu (CCKA), Klinikum Kempten, Kempten Germany
,
Diana Lüftner
8   Immanuel Hospital Märkische Schweiz & Immanuel Campus Rüdersdorf, Medical University of Brandenburg Theodor-Fontane, Rüdersdorf bei Berlin, Germany
,
Markus Wallwiener
9   Department of Gynecology, Halle University Hospital, Halle, Germany
,
Volkmar Müller
10   Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
,
Matthias W. Beckmann
5   Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Germany
11   Bavarian Center for Cancer Research (BZKF), Erlangen, Germany
,
Erik Belleville
12   ClinSol GmbH & Co KG, Würzburg, Germany
,
Hanna Huebner
5   Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Germany
,
Sabrina Uhrig
5   Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Germany
,
Chloë Goossens
5   Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Germany
,
Theresa Link
13   Department of Gynecology and Obstetrics, Carl Gustav Carus Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany
14   National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Carl Gustav Carus Faculty of Medicine and University Hospital, Technical University of Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
15   German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
,
Carsten Hielscher
16   Gynäkologie Kompetenzzentrum – Onkologisches Zentrum Stralsund, Germany
,
Christoph Mundhenke
17   Department of Gynecology and Obstetrics, Klinik Hohe Warte, Bayreuth, Germany
,
Christian Kurbacher
18   Department of Gynecology I (Gynecologic Oncology), Gynecologic Center Bonn-Friedensplatz, Bonn, Germany
,
Rachel Wuerstlein
19   Breast Center and CCC Munich, Dept of Gynecology and Obstetrics, University Hospital LMU Munich, Munich, Germany
,
Michael Untch
20   Department of Gynecology and Obstetrics, Helios Clinics Berlin-Buch, Berlin, Germany
,
Wolfgang Janni
21   Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany
,
Florin-Andrei Taran
22   Department of Gynecology and Obstetrics, University Hospital Freiburg, Freiburg, Germany
,
Laura L. Michel
23   National Center for Tumor Diseases, Heidelberg University Hospital, German Cancer Research Center (DKFZ), Heidelberg, Germany
,
Michael P. Lux
24   Department of Gynecology and Obstetrics, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, Germany; St. Vincenz Kliniken Salzkotten + Paderborn, Paderborn, Germany
,
Diethelm Wallwiener
1   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
,
Sara Y. Brucker
1   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
,
Tanja N. Fehm
25   Department of Gynecology and Obstetrics, Düsseldorf University Hospital, Düsseldorf, Germany
26   Center for integrated oncology Aachen Bonn Köln Düsseldorf, Düsseldorf, Germany
,
Lothar Häberle
5   Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–Nuremberg, Germany
27   Biostatistics Unit, Department of Gynecology and Obstetrics, Erlangen University Hospital, Erlangen, Germany
,
Andreas Schneeweiss
23   National Center for Tumor Diseases, Heidelberg University Hospital, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Abstract

Background With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry.

Methods Patients with information available on the first three therapy lines were selected from the German PRAEGNANT registry (NCT02338167). Attrition was determined for each therapy line using competing risk analyses, with the start of the next therapy line or death as endpoints. Additionally, a simple attrition rate was calculated based on the proportion of patients who completed therapy but did not start the next therapy line.

Results Competitive risk analyses were performed on 3988 1st line, 2651 2nd line and 1866 3rd line patients. The probabilities of not starting the next therapy line within 5 years after initiation of 1st, 2nd and 3rd line therapy were 30%, 24% and 24% respectively. Patients with HER2-positive disease had the highest risk for attrition, while patients with HRpos/HER2neg disease had the lowest risk. Attrition rates remained similar across molecular subgroups in the different therapy lines.

Conclusion Attrition affects a large proportion of patients with aBC, which should be considered when planning novel therapy concepts that specifically address the sequencing of therapies. Taking attrition into account could help understand treatment effects resulting from sequential therapies and might help develop treatment strategies that specifically aim at maintaining quality of life.

Zusammenfassung

Hintergrund Therapien zur Behandlung von fortgeschrittenem Brustkreb sind zunehmend effektiver geworden. Dies bedeutet auch, dass Therapiesequenzen immer wichtiger werden. Manche Patientinnen brechen aber eine Therapiesequenz wegen der Verschlechterung der Lebensqualität ab. Es gibt nur wenige Real-World-Daten zum Problem des Therapieabbruchs. Diese Studie untersucht Therapieabbrüche für die ersten 3 Therapielinien in einem Register mit Real-World-Daten.

Methoden Es wurden Patientinnen ausgewählt, für die Informationen im deutschen PRAEGNANT-Register zu den ersten 3 Therapielinien (NCT02338167) vorlagen. Die Therapieabbruchraten für jede Therapielinie wurde bestimmt mithilfe konkurrierender Risikoanalysen. Endpunkte waren der Beginn der nächsten Therapielinie oder der Tod. Es wurde auch eine einfache Abbruchrate berechnet, die auf den Prozensatz der Patientinnen beruhte, die eine Therapielinie abgeschlossen hatten, aber die nächste Therapielinie nicht anfingen.

Ergebnisse Konkurrierende Risikoanalysen wurden für 3988 Erstlinientherapie-Patientinnen, 2651 Zweitlinientherapie-Patientinnen und 1866 Drittlinientherapie-Patientinnen durchgeführt. Die Wahrscheinlichkeiten, dass Patientinnen die nächste Therapielinie nicht innerhalb von 5 Jahren nach Beginn der Erstlinien-, Zweitlinien- oder Drittlinientherapie begannen, betrugen jeweils 30%, 24% bzw. 24%. Das höchste Abbruchrisiko hatten Patientinnen mit HER2+ Erkrankung, wohingegen das Abbruchrisiko bei Patientinnen mit HR+/HER2− Brustkrebs am niedrigsten war. Die Abbruchraten waren in den verschiedenen Therapielinien über alle molekularen Subgruppen hinweg ähnlich.

Schlussfolgerung Therapieabbruch betrifft eine Vielzahl von Patientinnen mit fortgeschrittenem Brustkrebs. Dies sollte bei der Planung von neuartigen Therapiekonzepten, die speziell die Sequenzierung von Therapien zum Fokus haben, beachtet werden. Die Berücksichtigung von Therapieabbrüche könnte zu einem besseren Verständnis der Auswirkungen von sequenziellen Therapien führen und bei der Entwicklung von Behandlungsstrategien helfen, die konkret das Ziel haben, die Lebensqualität aufrechtzuhalten.

Keywords

advanced breast cancer - de novo metastatic breast cancer - recurrent breast cancer metastases - clinical trials

Schlüsselwörter

fortgeschrittener Brustkrebs - de novo metastasierter Brustkrebs - Brustkrebsrezidiv mit Metastasen - klinische Studien

Supplementary Material

    Supplementary Tables

    • Supplementary Table S1: Data categories recorded in the PRAEGNANT study.

    • Supplementary Table S2: Patient characteristics according to molecular subtype in the 1st therapy line.

    • Supplementary Table S3: Patient characteristics according to molecular subtype in the 2nd therapy line.

    • Supplementary Table S4: Patient characteristics according to molecular subtype in the 3rd therapy line.

    • Supplementary Table S5: Simple attrition rates for patients who completed the 1st therapy line according to patient/tumor characteristics.

    • Supplementary Table S6: Simple attrition rates for patients who completed the 2nd therapy line according to patient/tumor characteristics.

    • Supplementary Table S7: Simple attrition rates for patients who completed the 3rd therapy line according to patient/tumor characteristics.

    Supplementary Figures

    • Supplementary Fig. S1: Patient flow chart for the patient populations in the first line: Population 1CR, population 1ATR. CR: competing risk, ATR: simple attrition population.

    • Supplementary Fig. S2: Patient flow chart for the patient population in the second line: Population 2CR, and population 2ATR. CR: competing risk, ATR: simple attrition population.

    • Supplementary Fig. S3: Patient flow chart for the patient population in the third line: Population 3CR, and population 3ATR. CR: competing risk, ATR: simple attrition population.

  • Supporting Information


Publication History

Received: 10 January 2024

Accepted: 12 March 2024

Article published online:
29 May 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/)

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Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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