Abstract RF7-06: Primary results of Ambre, a randomized phase 3comparing mono-chemotherapy (ct) vs abemaciclib + endocrine therapy (et) in hr+/her2- advanced breast cancer (abc) with high visceral tumor burden

Abstract Background: Patients with HR+/HER2- ABC and visceral crisis were excluded from CDK4/6 inhibitor pivotal trials in fist line, and CT remains an option in these patients. Methods: The AMBRE trial (NCT04158362) assessed the efficacy of abemaciclib + ET compared to CT in pts with high visceral tumor burden. Eligible patients had HR+/HER2– ABC, ECOG 0–2, measurable disease, no prior systemic therapy for ABC, and high visceral burden (≥2 visceral sites, ≥3 lesions in one organ, or visceral disease with LDH ULN). Pts were randomized 1:1 to abemaciclib 150 mg BID + ET (letrozole or fulvestrant (based ET sensitivity) ± OFS) or CT at investigator’s choice: weekly paclitaxel (80 mg/m2) or capecitabine (2000–2500 mg/m2/day, d1–14 q21d). The primary endpoint was PFS; 118 events provided 80% power to detect an increase in median PFS from 8 to 13 months (HR=0.6, α=0.05). Secondary endpoints included PFS2, OS, ORR, DoR, safety, and QoL. Circulating Tumors Cells (CTC) count was performed (CellSearch®) at baseline, at Day 21(D1C2) and at progression. Results 180 patients were enrolled (abemaciclib: n=91; CT: n=89; 33.7% paclitaxel, 66.3% capecitabine) from 06.2020 to 07.2024. Median follow-up was ∼26 months. Baseline characteristics were balanced: median age 62.5 years, 77.2% with liver metastases, 38% were ET resistant, 62% ET sensitive, including 27% with de-novo metastatic disease. Median PFS was 13.9 months in abemaciclib arm versus 7.0 months in CT arm (HR=0.67, 95% CI 0.46 to 0.98, p=0.035). The PFS curves diverged as early at 4 months. DoR was significantly longer with abemaciclib (HR=0.46, p=0.023). No statistically significant difference was observed in ORR, QoL, PFS2 and OS. No new safety signal was observed. At baseline, the median number of CTCs was 5 (range 0-556). The prognostic value of CTC count was confirmed and CTC count changes under treatment showed similar patterns across study arms. Other translational research with ctDNA (ESR1 and PIK3CA) are ongoing in order to better characterize this population with high burden disease and their impact according to treatment arm. Conclusions: AMBRE demonstrates that Abemaciclib + ET significantly improves PFS over CT in first-line treatment of HR+/HER2– ABC with high visceral tumor burden and high CTC count, supporting its use as a standard option in this setting. Clinical trial identification NCT04158362 Legal entity responsible for the study UNICANCER UCBG Financial support: Lilly Citation Format: V. Dieras, F. C. Bidard, L. Roca, J. Pierga, T. Bachelot, I. Desmoulins, C. Jouannaud, X. Durando, C. Delbado, S. Lavau-Denes, F. Minne, A. C. Hardy-Bessard, K. Bourcier, O. Derbel, J. Grenier, F. Clatot, S. Renault, J. Lemonnier, C. Vissac-Sabatier, J. Péron, G. Freyer. Primary results of Ambre, a randomized phase 3comparing mono-chemotherapy (ct) vs abemaciclib + endocrine therapy (et) in hr+/her2- advanced breast cancer (abc) with high visceral tumor burden abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF7-06.