Amcenestrant vs Standard Endocrine Therapy in ER-Positive, HER2-Negative Advanced Breast Cancer

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In the phase II AMEERA-3 trial reported in the Journal of Clinical Oncology, Sara M. Tolaney, MD, MPH, and colleagues found that the selective estrogen receptor degrader amcenestrant did not improve progression-free survival vs physician’s choice of endocrine therapy in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer whose disease had progressed after no more than two prior lines of endocrine therapy.

Sara M. Tolaney, MD, MPH

Sara M. Tolaney, MD, MPH

Study Details

In the open-label trial, 290 patients from sites in 22 countries were randomly assigned between October 2019 and February 2021 to receive amcenestrant at 400 mg once daily (n = 143) or single-agent endocrine therapy of physician’s choice (TPC group; n = 147, including fulvestrant in 132, an aromatase inhibitor in 10, and tamoxifen in 5). Overall, 82% of patients in each group had received one prior line of endocrine therapy and 6% to 7% had received no prior endocrine therapy in the advanced setting. The primary endpoint was progression-free survival on independent central review.

Progression-Free Survival

Median follow-up was 11.2 months (interquartile range = 5.7­–16.5 months). Median progression-free survival was 3.6 months (95% confidence interval [CI] = 2.0–3.9 months) in the amcenestrant group vs 3.7 months (95% CI = 2.0–4.9 months) in the TPC group (hazard ratio [HR] = 1.05, 95% CI = 0.79–1.4, P = .644). Rates at 6 and 12 months were 35.5% vs 37.6% and 20.4% vs 24.6%, respectively.

Among 65 vs 55 patients with baseline ESR1 mutations, median progression-free survival was 3.7 months (95% CI = 1.9–7.2 months) in the amcenestrant group vs 2.0 months (95% CI = 1.9–4.3 months) in the TPC group (stratified HR = 0.9, 95% CI = 0.57–1.44). Among patients with wild-type ESR1, median progression-free survival was 3.5 months (95% CI = 2.0–3.7 months) with amcenestrant vs 3.9 months (95% CI = 3.6–9.2 months) with endocrine therapy (stratified HR = 1.30, 95% CI = 0.88 to 1.93).

Overall survival data were immature. At data cutoff, death had occurred in 40 patients in the amcenestrant group and 46 in the TPC group (HR = 0.91, 95% CI = 0.59–1.40).


  • Amcenestrant did not improve progression-free survival vs physician choice of endocrine therapy.
  • A numeric benefit was observed among patients with an ESR1 mutation.

Adverse Events

Grade ≥ 3 adverse events occurred in 21.7% of patients in the amcenestrant group vs 15.6% of the TPC group. Serious adverse events occurred in 16.1% vs 10.2% of patients. Treatment-related adverse events led to discontinuation in two patients in the amcenestrant group (dyspepsia and rash in one each). No clinically significant treatment-related cardiac or ocular adverse events were observed in the amcenestrant group. Adverse events led to death in one patient in the TPC group, due to pneumonia considered unrelated to treatment.

The investigators concluded, “AMEERA-3 did not meet its primary objective of improved progression-free survival with amcenestrant vs [physician’s choice of endocrine therapy] although a numerical improvement in progression-free survival was observed in patients with a baseline ESR1 mutation. Efficacy and safety with amcenestrant were consistent with the standard of care for second-/third-line endocrine therapy for ER-positive/HER2-negative advanced breast cancer.”

Dr. Tolaney, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Sanofi. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.