Amcenestrant Does Not Reduce Risk of Disease Progression or Death in ER+/HER2- Breast Cancer

An update from the phase 2 AMEERA-3 clinical trial shows that amcenestrant does not improve progression-free survival in ER-positive, HER2-negative breast cancer.

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Treatment with amcenestrant, did not demonstrate progression-free survival (PFS) improvement versus physician’s choice of endocrine therapy in patients with locally advanced or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer who progressed on or after hormonal therapies, missing the primary end point of the phase 2 AMEERA-3 clinical trial.1

An update from the study announced by Sanofi also noted that no new safety signals were observed and the safety profile of amcenestrant appeared consistent with prior studies.

“This phase 2 trial evaluated amcenestrant as a monotherapy in a patient population with advanced disease where limited treatment options remain. While we are disappointed with the AMEERA-3 results, we continue to investigate amcenestrant in patients with earlier stages of breast cancer with different tumor profiles and where different standard-of-care treatments are used,” said John Reed, MD, PhD, head of research and development at Sanofi, in a press release.

Amcenestrant is an investigational optimized oral selective estrogen receptor degrader. In the AMEERA-3 trial (NCT04059484), a total of 367 patients with ER-positive, HER2-negative advanced or metastatic breast cancer who were previously exposed to hormonal therapies were included to receive the investigational SERD. The study was conducted in an open-label and randomized fashion to evaluate PFS along with the secondary end points of overall survival, objective response rate, disease control rate, clinical benefit rate, duration of response, PFS according to ESR1 mutation status, pharmacokinetics, patient-reported outcomes, and the number of patients with treatment-emergent adverse events.2

Screening in the study lasted up to 4 weeks and treatment included at least 1 cycle of amcenestrant for 28 days. The agent was administered daily, orally under fed or fast condition. In the comparator arm, patients were treated with either fulvestrant, anastrozole

letrozole, exemestane, or tamoxifen. All study treatment was continued until unacceptable toxicity, disease progression, death, or upon a patient’s request. Following the treatment cycle, patients report to an end-of-treatment visit within 30 days of last dose of amcenestrant or physician’s choice of endocrine therapy.

Patients included in the study were those aged 18 years or older with histological or cytological diagnosis of breast cancer. All patients were required to have locally advanced disease that is ER-positive and HER2-negative. In addition, patients must have received no more than 1 prior chemotherapeutic or 1 targeted therapy regimen for advanced/metastatic disease. Prior treatment with a CDK 4/6 inhibitor was another requirement as was progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy but after the first 2 years, or with a relapse within 12 months following adjuvant endocrine therapy.

The study excluded patients with an ECOG performance status of ≥ 2; medical history or ongoing gastrointestinal disorders that may impact the absorption of amcenestrant; another cancer; severe, uncontrolled systemic disease at screening; known brain metastases that are untreated, symptomatic, or require therapy to control symptom; and inadequate hematological, coagulation, renal, and liver functions.

In terms of prior treatment, patients were excluded from the study if received a mammalian target of rapamycin inhibitors or any other SERD other than fulvestrant within 3 months before the study, agents that have may inhibit UGT less than 2 weeks before randomization, a strong CYP3A inducers within 2 weeks before randomization, anticancer agent within 3 weeks of randomization, and those who were receiving ongoing treatment with agents that are sensitive substrate of organic anion transporting polypeptide 1B1/B3.

Assessment of data in the AMEERA-3 trial is ongoing and the company is working with the study’s investigators to publish the full results. Outside of AMEERA-3, amcenestrant is being assessed in combination with palbociclib (Ibrance) as frontline treatment for patients with ER-positive, HER2-negaitve breast cancer (AMEERA-5; NCT04478266) as well as in the AMEERA-6 study of amcenestrant versus tamoxifen in patients with hormone receptor-positive early breast cancer who discontinued adjuvant aromatase inhibitor therapy due to treatment-related toxicity (NCT05128773).1,3,4


1. Sanofi provides update on Phase 2 study evaluating amcenestrant in ER+/HER2- advanced or metastatic breast cancer. News release. Sanofi. March 14, 2022. Accessed March 14, 2022.

2. Phase 2 study of amcenestrant (SAR439859) versus physician's choice in locally advanced or metastatic ER-positive breast cancer (AMEERA-3). Updated March 7, 2022. Accessed March 14, 2022.

3. Amcenestrant (SAR439859) plus palbociclib as first line therapy for patients with ER (+) HER2(-) advanced breast cancer (AMEERA-5). Updated December 16, 2021. Accessd March 14, 2022.

4. Study of amcenestrant (SAR439859) versus tamoxifen for patients with hormone receptor-positive (HR+) early breast cancer, who have discontinued adjuvant aromatase inhibitor therapy due to treatment-related toxicity (AMEERA-6). Updated February 20, 2022. Accessed March 14, 2022.

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