Abstract PO3-18-10: Impact of age and ovarian function suppression (OFS) on endocrine response to short preoperative endocrine therapy (ET): Results from the multicenter WSG-ADAPTcycle trial (n=5,290)

Abstract Background In HR+/HER2- early breast cancer (EBC), short preoperative endocrine therapy (ET) offers a promising tool for assessment of ET-efficacy based on Ki67-decrease after 2-4 weeks of treatment. Low post-endocrine Ki67 (Ki67post) is associated with good prognosis in several large prospective trials. WSG-ADAPT demonstrated that Ki67post is a promising tool for decision making in cases with uncertain adjuvant chemotherapy indication, e.g., in premenopausal patients (pts.) with N0 and Recurrence Score (RS, Oncotype DX®) RS 16-25 or N1 and RS ≤25. Preliminary results from the phase III ADAPTcycle trial indicated higher efficacy of preoperative ET in premenopausal pts. if ovarian function suppression (OFS) was used together with tamoxifen (TAM) or aromatase inhibitors (AI). In the ADAPTcycle screening population, we are now able to validate these results and investigate the influence of age subgroups, Recurrence Score, and individual biological markers, as well as OFS on ET-response. Methods In ADAPTcycle (n=5,290 screened until 06/23 at 84 sites in Germany), N0-1 pts. with RS >25 or N2-3 pts with RS ≤25 and ET-response (Ki67post ≤10%) were randomized to (neo)adjuvant standard chemotherapy (CT) or ribociclib + AI +/- GnRH-analog (n=1,670 randomized). Participation of premenopausal pts. with N1-disease and RS ≤25 or N0 and RS 16-25 was allowed irrespective of ET-response, but randomization recommended only for ET-responders. Use of OFS + TAM or AI for ET response assessment in the preoperative phase was protocol-recommended. This analysis includes all patients with baseline RS and data on ET-response. Ki67-response is defined as Ki67post ≤10% (central pathology assessment) after 2-4 weeks of therapy (OFS-use recommended for 4 weeks). ER-, PR-, and HER2-levels are analyzed by IHC and mRNA. Results Results on ET-response according to age and clinicopathological as well as tumor biological characteristics will be presented at the meeting. So far, ADAPTcycle with >5,000 pts. screened is the largest trial worldwide to look at ET response assessment in pre- and postmenopausal pts. with HR+/HER2- EBC. The results thus have the potential to impact clinical practice. Contact Information oleg.gluz@wsg-online.com Citation Format: Oleg Gluz, Matthias Christgen, Ulrike Nitz, Sherko Küemmel, Michael Braun, Marc Thill, Rachel Wuerstlein, Pauline Wimberger, Andreas Hartkopf, Christian Schem, Matthias Zaiss, Vesna Bjelic-Radisic, Marianne Just, Kristina Veselinovic, Myriam Vincent, Monika Graeser, Katja Krauss, Oliver Hoffmann, Kerstin Lüdtke-Heckenkamp, Ronald Kates, Christine zu Eulenburg, Peter Schmid, Rick Baehner, Hans-Heinrich Kreipe, Nadia Harbeck. Impact of age and ovarian function suppression (OFS) on endocrine response to short preoperative endocrine therapy (ET): Results from the multicenter WSG-ADAPTcycle trial (n=5,290) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-10.