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AMEERA-4: a randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast
Mario Campone1, François-Clément Bidard2,3,4, Patrick Neven5
1Institut de Cancérologie de l'Ouest, René Gauducheau, Boulevard Jacques Monod, 44805, Saint-Herblain, France. mario.campone@ico.unicancer.fr.
Background:
Window-of-opportunity (WOO) studies provide insights into the clinical activity of new drugs in breast cancer.
Methods:
AMEERA-4 (NCT04191382) was a WOO study undertaken to compare the pharmacodynamic effects of amcenestrant, a selective estrogen receptor degrader, with those of letrozole in postmenopausal women with newly diagnosed, operable estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. Women were randomized (1:1:1) to receive amcenestrant 400 mg, amcenestrant 200 mg, or letrozole 2.5 mg once daily for 14 days before breast surgery. The primary endpoint was change in Ki67 between baseline and Day 15 (i.e., day of surgery).
Results:
Enrollment was stopped early because of slow recruitment, in the context of the COVID-19 pandemic. The modified intent-to-treat population consisted of 95 study participants with baseline and post-treatment Ki67 values, whereas the safety population included 104 participants who had received at least one dose of study medication. Relative change from baseline in Ki67 was - 75.9% (95% confidence interval [CI] - 81.9 to - 67.9) for amcenestrant 400 mg, - 68.2% (- 75.7 to - 58.4) for amcenestrant 200 mg, and - 77.7% (- 83.4 to - 70.0) for letrozole (geometric least-squares mean [LSM] estimates). Absolute change in ER H-score from baseline (LSM estimate) was - 176.7 in the amcenestrant 400 mg arm, - 202.9 in the amcenestrant 200 mg arm, and - 32.5 in the letrozole arm. There were no Grade ≥ 3 treatment-related adverse events.
Conclusions:
Both amcenestrant and letrozole demonstrated antiproliferative activity in postmenopausal women with previously untreated, operable ER+/HER2- breast cancer and had good overall tolerability.
Trial Registration:
ClinicalTrials.gov, NCT04191382 https://clinicaltrials.gov/ct2/show/NCT04191382 . Registered 9 December 2019.
Insights
This study compared amcenestrant, a selective estrogen receptor degrader, with letrozole in postmenopausal women with breast cancer. Both drugs showed antiproliferative effects, with amcenestrant demonstrating potent activity.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Window-of-opportunity (WOO) studies assess new breast cancer drug activity.
- Estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer is a key focus in endocrine therapy research.
Purpose of the Study:
- To compare the pharmacodynamic effects of amcenestrant (a selective estrogen receptor degrader) versus letrozole.
- To evaluate antiproliferative activity in postmenopausal women with newly diagnosed, operable ER+/HER2- breast cancer.
Main Methods:
- The AMEERA-4 study (NCT04191382) randomized 95 participants (modified intent-to-treat) to amcenestrant (400mg or 200mg) or letrozole (2.5mg) for 14 days pre-surgery.
- Primary endpoint: change in Ki67 proliferation marker from baseline to Day 15.
- Safety population included 104 participants receiving at least one dose.
Main Results:
- Amcenestrant 400mg showed a -75.9% relative change in Ki67, amcenestrant 200mg showed -68.2%, and letrozole showed -77.7%.
- Absolute change in ER H-score was -176.7 for amcenestrant 400mg, -202.9 for amcenestrant 200mg, and -32.5 for letrozole.
- No Grade ≥3 treatment-related adverse events were reported.
Conclusions:
- Both amcenestrant and letrozole demonstrated significant antiproliferative activity.
- Amcenestrant and letrozole exhibited good overall tolerability in this patient population.
