Amcenestrant demonstrated robust Ki67 reductions in patients with postmenopausal ER+/HER2- primary breast cancer in the neoadjuvant setting, according to an abstract presented at the ASCO 2022 Annual Meeting.

Amcenestrant is an oral selective estrogen receptor degrader that both antagonizes and degrades the estrogen receptor which leads to an inhibition of the estrogen receptor signaling pathway. 

AMEERA-4 is a phase 2 preoperative window-of-opportunity study that evaluated the pharmacodynamic activity of amcenestrant 400 mg, amcenestrant 200 mg, and letrozole 2.5 mg given 14 days before surgery. The primary endpoint was the antiproliferatation activity as measured using the change in Ki67 levels between baseline and after 14 days of treatment. 

A total of 105 patients were randomized. Thirty-four received amcenestrant 400 mg daily, 36 received amcenestrant 200 mg daily, and 35 received letrozole 2.5 mg daily. 

The geometric least squares mean estimate of Ki67 reduction was 75.9% (95% CI, 67.9-81.9) for amcenestrant 400 mg, 68.2% (95% CI, 58.4-75.7) for amcenestrant 200 mg, and 77.7% (95% CI, 70.0-83.4) for letrozole.

The incidence of treatment-related adverse events was 21.2% for amcenestrant 400 mg, 22.2% for amcenestrant 200 mg, and 25.7% for letrozole. No grade 3 or higher treatment-related adverse events occurred.

In summary, both doses of amcenestrant showed significant Ki67 reductions, strongly engaged the estrogen receptor target, and continued to show a favorable safety profile. Based on results from this study, amcenestrant at the 200 mg once daily dose will be the chosen dose for the AMEERA-6 study investigating amcenestrant in the adjuvant setting.

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Disclosures: Authors declared financial ties to drugmakers. See full study for details.