Abemaciclib Plus Endocrine Therapy for HR-Positive, HER2-Negative Advanced Breast Cancer
Key Clinical Takeaways
- Design/Population: The AMBRE trial randomized 180 patients with untreated HR-positive, HER2-negative advanced breast cancer and high visceral tumor burden to receive abemaciclib plus endocrine therapy or physician’s choice chemotherapy. High visceral burden required ≥ 2 visceral sites, ≥3 lesions in one organ, or elevated LDH, and circulating tumor cells were assessed longitudinally.
- Key Outcomes: Abemaciclib plus endocrine therapy significantly improved progression-free survival compared with chemotherapy (13.9 vs 7 months; HR, 0.67). Duration of response also favored abemaciclib, while ORR, OS, and quality-of-life outcomes were similar between arms.
- Clinical Relevance: These findings support abemaciclib plus endocrine therapy as an effective first-line option for HR-positive, HER2-negative advanced breast cancer with high visceral tumor burden, a population often excluded from CDK4/6 inhibitor trials. Safety was consistent with expected profiles, and ongoing translational analyses may refine patient selection.
Results from the phase 3 AMBRE trial demonstrate that abemaciclib plus endocrine therapy significantly improves progression-free survival (PFS) compared with investigators choice chemotherapy among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer and high visceral tumor burden.
These findings were presented by Véronique Dieras, MD, Eugene Marquis Center, Rennes, France, at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas.
In this study, 180 previously untreated patients were randomized 1:1 to receive either 150 mg of twice daily abemaciclib plus endocrine therapy (letrozole or fulvestrant based on sensitivity, with optional ovarian function suppression) or chemotherapy (weekly paclitaxel or capecitabine). High visceral burden was defined as ≥2 visceral sites involved, ≥3 lesions in a single organ, or visceral disease with lactate dehydrogenase above the upper limit of normal.
The primary end point was PFS. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of response, quality of life, and safety. Circulating tumor cell analysis was performed at baseline, day 21, and progression.
At a median follow-up of 26 months, median PFS was 13.9 months in the abemaciclib arm and 7 months in the chemotherapy arm (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.46 to 0.98; P = .035). PFS curves separated as early as 4 months, and duration of response was significantly longer with abemaciclib (P = .023). No statistically significant differences were observed in ORR, OS, PFS2, or quality-of-life measures. Safety findings were consistent with the known profiles of abemaciclib and chemotherapy, with no new safety signals identified.
Baseline median circulating tumor cell count was 5 (range, 0 to 556), confirming its prognostic value in this population. Circulating tumor cell dynamics during treatment were similar across study arms. Additional translational analyses including ctDNA (ESR1 and PIK3CA) are ongoing.
Source:
Dieras V, Bidard FC, Roca L, et al. Primary results of Ambre, a randomized phase 3 comparing mono-chemotherapy (ct) vs abemaciclib + endocrine therapy (et) in hr+/her2- advanced breast cancer (abc) with high visceral tumor burden. Presented at SABCS 2025. December 9 - 12, 2025. San Antonio, Texas. Abstract RF7-06
