AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer

• Published in: Journal of clinical oncology Vol. 41; no. 24; pp. 4014 - 4024
• Main Authors: Tolaney, Sara M, Chan, Arlene, Petrakova, Katarina, Delaloge, Suzette, Campone, Mario, Iwata, Hiroji, Peddi, Parvin F, Kaufman, Peter A, De Kermadec, Elisabeth, Liu, Qianying, Cohen, Patrick, Paux, Gautier, Wang, Lei, Ternès, Nils, Boitier, Eric, Im, Seock-Ah
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 20-08-2023
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast Neoplasms - pathology; Female; Humans; ORIGINAL REPORTS; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.22.02746

Amcenestrant (oral selective estrogen receptor degrader) demonstrated promising safety and efficacy in earlier clinical studies for endocrine-resistant, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (aBC).
In AMEERA-3 (ClinicalTrials.gov identifier: NCT04059484), an open-label, worldwide phase II trial, patients with ER+/HER2- aBC who progressed in the (neo)adjuvant or advanced settings after not more than two previous lines of endocrine therapy (ET) were randomly assigned 1:1 to amcenestrant or single-agent endocrine treatment of physician's choice (TPC), stratified by the presence/absence of visceral metastases, previous/no treatment with cyclin-dependent kinase 4/6 inhibitor, and Eastern Cooperative Oncology Group performance status (0/1). The primary end point was progression-free survival (PFS) by independent central review, compared using a stratified log-rank test (one-sided type I error rate of 2.5%).
Between October 22, 2019, and February 15, 2021, 290 patients were randomly assigned to amcenestrant (n = 143) or TPC (n = 147). PFS was numerically similar between amcenestrant and TPC (median PFS [mPFS], 3.6
3.7 months; stratified hazard ratio [HR], 1.051 [95% CI, 0.789 to 1.4]; one-sided
= .643). Among patients with baseline mutated
; (n = 120 of 280), amcenestrant numerically prolonged PFS versus TPC (mPFS, 3.7
2.0 months; stratified HR, 0.9 [95% CI, 0.565 to 1.435]). Overall survival data were immature but numerically similar between groups (HR, 0.913; 95% CI, 0.595 to 1.403). In amcenestrant versus TPC groups, treatment-emergent adverse events (any grade) occurred in 82.5% versus 76.2% of patients and grade ≥3 events occurred in 21.7% versus 15.6%.
AMEERA-3 did not meet its primary objective of improved PFS with amcenestrant versus TPC although a numerical improvement in PFS was observed in patients with baseline
mutation. Efficacy and safety with amcenestrant were consistent with the standard of care for second-/third-line ET for ER+/HER2- aBC.