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

Nadia Harbeck Breast Center, Dept. Obstetrics & Gynecology, University of Munich (LMU) and CCCLMU and West German Study Group, Munich, Germany info_outline Nadia Harbeck, Oleg Gluz, Matthias Christgen, Michael Braun, Marc Thill, Pauline Wimberger, Kerstin Luedtke-Heckenkamp, Monika Graeser, Felix Hilpert, Vesna Bjelic-Radisic, Katja Krauss, Mathias Warm, Matthias R. Zaiss, Andreas D. Hartkopf, Marianne Just, Hans Heinrich Kreipe, Ulrike Nitz, Christine zu Eulenburg, Rachel Wuerstlein, Sherko Kuemmel

Authors Nadia Harbeck Breast Center, Dept. Obstetrics & Gynecology, University of Munich (LMU) and CCCLMU and West German Study Group, Munich, Germany info_outline Nadia Harbeck, Oleg Gluz, Matthias Christgen, Michael Braun, Marc Thill, Pauline Wimberger, Kerstin Luedtke-Heckenkamp, Monika Graeser, Felix Hilpert, Vesna Bjelic-Radisic, Katja Krauss, Mathias Warm, Matthias R. Zaiss, Andreas D. Hartkopf, Marianne Just, Hans Heinrich Kreipe, Ulrike Nitz, Christine zu Eulenburg, Rachel Wuerstlein, Sherko Kuemmel Organizations Breast Center, Dept. Obstetrics & Gynecology, University of Munich (LMU) and CCCLMU and West German Study Group, Munich, Germany, West German Study Group and Ev. Hospital Bethesda, Breast Center Niederrhein, Moenchengladbach, Germany and University Hospital Cologne, Cologne, Germany, Medical School Hannover, Institute of Pathology, Hannover, Germany, Interdisciplinary Breast Center, Rotkreuz-Clinics Munich, Munich, Germany, Breast Center, Agaplesion Markus Hospital, Frankfurt, Germany, Department of Gynecology and Obstetrics, TU Dresden, Dresden, Germany, Niels-Stensen-Kliniken, Franziskus-Hospital Harderberg, Georgsmarienhütte, Germany, Breast Center Niederrhein, Ev. Bethesda Hospital and Department of Gynecology, University Medical Center Hamburg and West German Study Group, Mönchengladbach, Germany, Breast Center Hamburg International, Hospital Jerusalem, Hamburg, Germany, Breast Unit, Helios University Clinic, University Witten-Herdecke, Wuppertal, Germany, Breast Center, Dept. Obstetrics & Gynecology, RWTH Aachen, Aachen, Germany, Breast Center Cologne-Holweide, Municipal Hospital Holweide, Cologne, Germany, Medical Practice for Oncology and Hematology, Freiburg, Germany, Department of Gynecology and Obstetrics, University of Tuebingen and University of Ulm, Tuebingen and Ulm, Germany, Oncological Specialist Practice Bielefeld, Bielefeld, Germany, Hanover Medical School, Institute of Pathology, Hannover, Germany, West German Study Group/Breast Center Niederrhein, Mönchengladbach, Germany, Medical Biometry and Epidemiology, UKE Hamburg, Hamburg, Germany, Breast Center, Dept. OB&GYN, University of Munich (LMU) and CCCLMU, West German Study Group, Munich, Germany, West German Study Group, Moenchengladbach, Germany and Clinics Essen-Mitte, Breast Center, Essen, Germany and Women’s Clinic, Charité Berlin, Berlin, Germany, Essen, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company 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.