ADAPTlate: A randomized, controlled, open-label, phase III trial on adjuvant dynamic marker—Adjusted personalized therapy comparing abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy in (clinical or genomic) high-risk, HR+/HER2- early breast cancer.
Authors: Oleg Gluz, Iris Scheffen, Tom Degenhardt, Norbert Walter Marschner, Matthias Christgen, Hans Heinrich Kreipe, Ulrike Nitz, Ronald E. Kates, Timo Schinkoethe, Monika Karla Graeser, Rachel Wuerstlein, Sherko Kuemmel, Lelia Bauer, Christian Schem, Tanja N. Fehm, Hans Neubauer, Nadia Harbeck
Journal: Journal of Clinical Oncology (2021)

TPS598 Background: The WSG ADAPT trial program addresses the individualization of (neo)adj. decision-making in EBC. The ADAPT umbrella trial established early predictive molecular surrogate markers for response after a 3-wk endocrine treatment (ET) to omit chemotherapy (CT) in a cohort of early high-risk HR+/HER2- pts. ADAPTlate seeks to improve adj. therapy for pts. at high risk for late disease recurrence, who completed definite locoregional therapy (with / without (neo-)adj. CT) and are under adj. ET. This high-risk population does not derive optimal benefit from standard ET, develops secondary ET resistance, and late recurrences. Methods: Prospective, multi-center, interventional, two-arm, open, randomized, controlled adj. phase III trial (NCT04565054) to investigate additional benefit from 2 years of the CDK4/6-inhibitor abemaciclib combined with ET compared to ET alone in pts. with high-risk HR+/HER2- EBC. Abemaciclib demonstrated to improve outcome in metastatic BC and even in EBC when given as part of primary therapy. Primary objective is to demonstrate superiority of iDFS of abemaciclib + ET vs. standard ET. Secondary objectives include OS, dDFS, occurrence of CNS metastases, QoL, and translational research. Recruitment started in 9/2020 to screen 1250 pts. and to randomize 903 pts. in a ratio 3:2. Until date of submission, 33 pts. were screened and 22 randomized. Pre-/postmenopausal pts. with histologically confirmed invasive HR+/HER2- EBC, 2-6 y after primary diagnosis, with either known high clinical risk (c/pN 2-3 OR high CTS score in pN 0-1 OR non-pCR after neoadj. CT in cN 1 or G3 tumors OR G3 and Ki-67 ≥ 40% in pN 0-1) or known high genomic risk (RS &gt;25 in c/pN 0, RS &gt;18 in c/pN 1 OR high risk Prosigna, EPclin or Mammaprint in pN 0-1) or intermediate clinical, but unknown genomic risk (luminal B-like (G3 or Ki-67 ≥20%) in c/pN 0-1 AND either RS &gt;25 in c/pN 0 or RS &gt;18 in c/p N1 in screening) will be eligible. Treatment duration is 2 years for the abemaciclib + ET (premenopausal: AI + GnRH) arm, followed by at least 3-6 years ET alone. Pts. in control arm will receive 5-8-years ET at investigator´s choice. ePROs are collected using CANKADO. Translational analyses: Exploratory tissue biomarker research to assess alterations in molecular markers. Liquid biopsies (CTC/ctDNA/ctRNA) will be assessed for mutations and gene expression relevant for HR+/HER2- EBC using an appropriate technology at time of testing. Conclusions: ADAPTlate seeks to evaluate whether Abemaciclib + ET is superior to ET alone in pts. with clinical or genomic high-risk EBC even 2-6 years after initial diagnosis. Translational research aims at assessing potential mechanisms of resistance to endocrine and/or CDK4/6 targeted therapy. Clinical trial information: NCT04565054.