AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib versus letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer
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Aditya Bardia1, Javier Cortes2, Sara A Hurvitz3
1Oncology/Hematology, Massachusetts General Hospital, Harvard Medical School, BHX-237, 55 Fruit Street, Boston, MA 02114, USA.
Background:
For estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), the current standard first-line treatment includes an aromatase inhibitor in combination with a cyclin-dependent kinase 4/6 inhibitor. When resistance occurs, often related to the occurrence of ESR1 mutations, selective estrogen receptor modulators or degraders (SERDs) may be used, alone or in combination regimens. Amcenestrant (SAR439859), an optimized oral SERD, has shown clinical antitumor activity in combination with palbociclib in patients with ER+/HER2- ABC and, as monotherapy, in patients with and without ESR1 mutations. Here, we describe the study design of AMEERA-5, an ongoing, prospective, phase 3, randomized, double-blind, multinational study comparing the efficacy and safety of amcenestrant plus palbociclib versus letrozole plus palbociclib in patients with advanced (locoregional recurrent or metastatic) ER+/HER2- breast cancer.
Methods:
Patients are pre-/postmenopausal women and men with no prior systemic therapy for ABC. The planned enrollment is 1066 patients. Patients are randomized 1:1 to either amcenestrant 200 mg plus palbociclib 125 mg or letrozole 2.5 mg plus palbociclib 125 mg. Amcenestrant, letrozole, and their matching placebos are taken once daily continuously; palbociclib is taken once daily for 21 days, followed by 7 days off-treatment for a 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or decision to stop treatment. Pre-/perimenopausal women and men receive goserelin subcutaneously. Randomization is stratified by de novo metastatic disease, menopausal status, and visceral metastases. The primary endpoint is progression-free survival. The key secondary endpoint is overall survival; others are safety, pharmacokinetics, and quality of life.
Conclusions:
AMEERA-5 is evaluating the efficacy and safety of amcenestrant in combination with palbociclib as first-line therapy in pre-/postmenopausal women and men with ER+/HER2- ABC.
Clinicaltrials Identifier:
NCT04478266.
Insights
The AMEERA-5 study compares amcenestrant plus palbociclib to letrozole plus palbociclib for advanced ER+/HER2- breast cancer. This trial evaluates a novel oral selective estrogen receptor degrader (SERD) as a potential new first-line treatment option.
Area of Science:
- Oncology
- Endocrinology
- Clinical Pharmacology
Background:
- Standard first-line treatment for ER+/HER2- advanced breast cancer (ABC) involves an aromatase inhibitor and a CDK4/6 inhibitor.
- Treatment resistance, often linked to ESR1 mutations, necessitates alternative therapies like selective estrogen receptor modulators or degraders (SERDs).
- Amcenestrant, an oral SERD, has demonstrated antitumor activity in ER+/HER2- ABC, both as monotherapy and in combination regimens.
Purpose of the Study:
- To evaluate the efficacy and safety of amcenestrant plus palbociclib compared to letrozole plus palbociclib as a first-line treatment for advanced ER+/HER2- breast cancer.
- To assess the potential of amcenestrant as an optimized oral SERD in a first-line setting for patients with advanced ER+/HER2- breast cancer.
Main Methods:
- The AMEERA-5 study is a prospective, phase 3, randomized, double-blind, multinational trial.
- 1066 pre-/postmenopausal women and men with no prior systemic therapy for ABC are randomized 1:1 to receive either amcenestrant 200 mg plus palbociclib 125 mg or letrozole 2.5 mg plus palbociclib 125 mg.
- Treatment continues until disease progression or unacceptable toxicity, with progression-free survival as the primary endpoint.
Main Results:
- This section is not applicable as the abstract describes the study design, not the results.
- The study is ongoing and will provide data on the comparative efficacy and safety of the two treatment arms.
Conclusions:
- The AMEERA-5 trial is evaluating amcenestrant plus palbociclib as a potential new first-line therapy for advanced ER+/HER2- breast cancer.
- The study aims to determine if this novel combination offers improved outcomes compared to the current standard of care.
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