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

Journal of Clinical Oncology, vol. 38, pp. TPS601

Abstract

TPS601 Background: The WSG ADAPT trial program represents the concept of individualization of (neo)-adjuvant decision-making in EBC in a subtype-specific manner. The first WSG ADAPT umbrella trial aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment. The goals of the WSG ADAPT trial program are early response assessment and subtype-specific therapy tailoring to those patients who are most likely to benefit. Methods: WSG-ADAPTcycle is a prospective, multi-center, interventional, two-arm, open-label, (neo)adjuvant, non-blinded, randomized, controlled phase III trial (NCT04055493). It investigates whether patients (pts.) with HR+/HER2- EBC identified during screening as intermediate risk (based on Oncotype DX and response to 3 weeks of preoperative endocrine therapy [ET]) derive additional benefit from 2 years of the CDK4/6 inhibitor ribociclib combined with ET compared to chemotherapy (CT) (followed by standard ET). Co-primary endpoints are disease-free survival (DFS) and distant DFS. It is planned to screen 5600 pts and to randomize 1670 pts in a 3:2 ratio (ribociclib + ET/CT). Study start was in July 2019 (80 sites, enrollment period 36 months) and until date of submission, 180 pts. have been screened and 40 randomized. Pts with HR+/HER2- EBC with clinically enhanced risk (cT2-4 or Ki67 20% or G3 or cN+) are eligible if they fulfill the ADAPT intermediate-risk group criteria: either Recurrence Score (RS) ≤25 and Ki67postendocrine>10%, RS >25 and Ki67postendocrine<10% in p/cN0-1 pts, or RS ≤25 and Ki67postendocrine<10% in c/pN2-3 pts. Treatment duration is 2 years for the ribociclib + ET (premenopausal: AI + GnRH) arm and 16-24 weeks for the CT arm; treatment is possible either in the neoadjuvant (ET + ribociclib duration 16 – 32 weeks) or adjuvant setting. ePROs are collected using CANKADO; ECG monitoring is performed using a novel cardiology-supported CANKADO-based eHealth method. Translational analyses: 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. Conclusions: ADAPTcycle seeks to evaluate whether endocrine-based therapy with ET and a CDK 4/6 inhibitor is superior to CT followed by ET in patients with luminal EBC who may be undertreated with ET alone (based on either lack of endocrine responsiveness or high tumor burden). Clinical trial information: 2018-003749-40 .

Authors 17

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

   University Hospital Cologne

   Affiliation as printed

   Breast Center Niederrhein, University Clinics Cologne and West German Study Group, Moenchengladbach, Germany;

3. Matthias Christgen

   Medizinische Hochschule Hannover

   Affiliation as printed

   Hannover Medical School, Hannover, Germany;

4. Monika Graeser

   Evangelisches Krankenhaus Bethesda Mönchengladbach

   Affiliation as printed

   Breast Center Niederrhein, Ev. Bethesda Hospital and West German Study Group, Mönchengladbach, Germany;

5. Felix Hilpert

   Krankenhaus Jerusalem

   Affiliation as printed

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

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

   RWTH Aachen University

   Affiliation as printed

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

7. Marc Thill

   Agaplesion Markus Hospital

   Affiliation as printed

   Breast Center, Agaplesion Markus Hospital, Frankfurt, Germany;

8. Mathias R. Warm

   Krankenhaus Köln-Holweide

   Affiliation as printed

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

9. Volkmar Müller

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

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

10. Michael Wilhelm Braun

    Rotkreuzklinikum München

    Affiliation as printed

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

11. Marianne Just
    Affiliation as printed

    Oncological Specialist Practice Bielefeld, Bielefeld, Germany;

12. Hans Heinrich Kreipe

    Medizinische Hochschule Hannover

    Affiliation as printed

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

13. Ulrike Anneliese Nitz

    Ludwig-Maximilians-Universität München

    Affiliation as printed

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

14. Ronald Ernest Kates

    Women‘s Healthcare Group

    Affiliation as printed

    West German Study Group, Moenchengladbach, Germany;

15. Timo Schinkoethe
    Affiliation as printed

    CANKADO Service GmbH, Munich, Germany;

16. Rachel Wuerstlein

    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;

17. Sherko Küemmel

    Kliniken Essen-Mitte

    Affiliation as printed

    Breast Center, Ev. Clinics Essen-Mitte and West German Study Group, Essen, Germany;