Adjuvant dynamic marker-adjusted personalized therapy comparing endocrine therapy plus ribociclib versus chemotherapy in intermediate-risk HR+/HER2- early breast cancer: ADAPTcycle.

Journal of Clinical Oncology, vol. 40, pp. TPS609

Abstract

TPS609 Background: The WSG ADAPT trial program focusses on individualization of (neo)-adjuvant decision-making in EBC in a subtype-specific manner. Clinical feasibility of the WSG ADAPT trial goals - early response assessment and subtype-specific therapy tailoring to those patients (pts) who are most likely to benefit - has recently been confirmed by the 5-years survival data of the ADAPT HR+/HER2- clinical trial. Methods: WSG-ADAPTcycle is a prospective, multi-center, interventional, two-arm, (neo)adjuvant, non-blinded, randomized, controlled phase III trial (NCT04055493) investigating whether treatment with the CDK4/6 inhibitor ribociclib (600mg/day) together with ET is superior to standard-chemotherapy (CT) in intermediate-risk HR+/HER2- EBC. Definition of intermediate-risk is either based on Oncotype DX and endocrine responder status (measured by Ki67-response after 2-4 weeks of induction endocrine therapy (ET)) or on low-intermediate baseline Ki67 and high estrogen receptor (ER)/progesterone receptor (PR)-expression (Dowsett et al. NPJ Breast Cancer 2020). Co-primary endpoints are DFS and dDFS. It is planned to screen 5600 pts and to randomize 1670 pts (1002 to ribociclib + ET; 668 to standard CT followed by ET). Study start was in July 2019 (88 sites, enrollment period 42 months) and until date of submission, 3079 pts have been screened and 811 randomized (490 ribociclib / 321 CT). Pre-/postmenopausal pts with histologically confirmed invasive HR+/HER2- EBC with high clinical risk (cT2-4 or Ki-67 20% or G3 or cN+) are eligible if they fulfil the ADAPT intermediate-risk criteria: Recurrence Score (RS) ≤25 plus several risk factors and poor ET responder, RS >25 and ET-responder in p/cN0-1 pts, or RS ≤25 with c/pN2-3 in ET-responder. Direct randomization of premenopausal patients (irrespective of ET-response) with c/pN0 and RS 16-25 or c/pN1 with RS 0-25 is allowed according to investigator´s decision; however, based on the ADAPT results, ET+ovarian function suppression alone is strongly recommended in ET-responders. Treatment duration is 2 years for the ribociclib + aromatase inhibitor (AI) (premenopausal: AI + GnRH)-arm and 16-24 weeks for the CT-arm; neoadjuvant or adjuvant treatment is allowed. The minimum 5-year follow-up phase includes standard adjuvant ET. ePROs are collected using CANKADO; ECG monitoring is performed using a novel eHealth method. Translational analyses: Tumor tissue will be collected prior to ET, after at least 3 weeks of ET, if residual tumor is diagnosed (neoadjuvant treatment), and at recurrence, to identify potential resistance markers. Exploratory tissue biomarker research will be conducted to assess alterations in molecular markers. In addition, ctDNA/ctRNA from optional blood samples will be assessed for mutations and gene expression relevant for HR+/HER2- EBC. Clinical trial information: NCT04055493.

Authors 20

1. Nadia Harbeck

   Ludwig-Maximilians-Universität München

   Affiliation as printed

   Breast Center, Dept. Obstetrics & Gynecology, University of Munich (LMU) and CCCLMU and West German Study Group, Munich, Germany;

2. Oleg Gluz

   Evangelisches Krankenhaus Bethesda Mönchengladbach · University Hospital Cologne

   Affiliation as printed

   West German Study Group and Ev. Hospital Bethesda, Breast Center Niederrhein, Moenchengladbach, Germany and University Hospital Cologne, Cologne, Germany;

3. Matthias Christgen

   Medizinische Hochschule Hannover

   Affiliation as printed

   Medical School Hannover, Institute of Pathology, Hannover, Germany;

4. Michael S Braun

   Rotkreuzklinikum München

   Affiliation as printed

   Interdisciplinary Breast Center, Rotkreuz-Clinics Munich, Munich, Germany;

5. Marc Thill

   Agaplesion Markus Hospital

   Affiliation as printed

   Breast Center, Agaplesion Markus Hospital, Frankfurt, Germany;

6. Pauline Wimberger

   Technische Universität Dresden

   Affiliation as printed

   Department of Gynecology and Obstetrics, TU Dresden, Dresden, Germany;

7. Kerstin Lüedtke-Heckenkamp
   Affiliation as printed

   Niels-Stensen-Kliniken, Franziskus-Hospital Harderberg, Georgsmarienhütte, Germany;

8. Monika Graeser

   Universität Hamburg · Women‘s Healthcare Group

   Affiliation as printed

   Breast Center Niederrhein, Ev. Bethesda Hospital and Department of Gynecology, University Medical Center Hamburg and West German Study Group, Mönchengladbach, Germany;

9. Felix Hilpert

   Krankenhaus Jerusalem

   Affiliation as printed

   Breast Center Hamburg International, Hospital Jerusalem, Hamburg, Germany;

10. Vesna Bjelic‐Radisic

    Witten/Herdecke University · Helios Universitätsklinikum Wuppertal

    Affiliation as printed

    Breast Unit, Helios University Clinic, University Witten-Herdecke, Wuppertal, Germany;

11. Katja Krauss Aachen Breast Center Dept. Obstetrics & Gynecology

    RWTH Aachen University

    Affiliation as printed

    Breast Center, Dept. Obstetrics & Gynecology, RWTH Aachen, Aachen, Germany;

12. Mathias R. Warm

    Krankenhaus Köln-Holweide

    Affiliation as printed

    Breast Center Cologne-Holweide, Municipal Hospital Holweide, Cologne, Germany;

13. Matthias R. Zaiss
    Affiliation as printed

    Medical Practice for Oncology and Hematology, Freiburg, Germany;

14. Andreas Daniel Hartkopf

    Universität Ulm · University of Tübingen

    Affiliation as printed

    Department of Gynecology and Obstetrics, University of Tuebingen and University of Ulm, Tuebingen and Ulm, Germany;

15. Marianne Just
    Affiliation as printed

    Oncological Specialist Practice Bielefeld, Bielefeld, Germany;

16. Hans Heinrich Kreipe

    Medizinische Hochschule Hannover

    Affiliation as printed

    Hanover Medical School, Institute of Pathology, Hannover, Germany;

17. Ulrike Anneliese Nitz

    Women‘s Healthcare Group

    Affiliation as printed

    West German Study Group/Breast Center Niederrhein, Mönchengladbach, Germany;

18. Christine zu Eulenburg

    University Medical Center Hamburg-Eppendorf

    Affiliation as printed

    Medical Biometry and Epidemiology, UKE Hamburg, Hamburg, Germany;

19. Rachel Wuerstlein

    Ludwig-Maximilians-Universität München

    Affiliation as printed

    Breast Center, Dept. OB&GYN, University of Munich (LMU) and CCCLMU, West German Study Group, Munich, Germany;

20. Sherko Küemmel

    Women‘s Healthcare Group · Kliniken Essen-Mitte · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    West German Study Group, Moenchengladbach, Germany and Clinics Essen-Mitte, Breast Center, Essen, Germany and Women’s Clinic, Charité Berlin, Berlin, Germany, Essen, Germany;