Randomized Phase III Study of Amcenestrant Plus Palbociclib Versus Letrozole Plus Palbociclib in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Primary Results From AMEERA-5
Javier Cortés, Sara A. Hurvitz, Joyce O’Shaughnessy, Suzette Delaloge, Hiroji Iwata, Hope S. Rugo, Patrick Neven, Dheepak Kanagavel, Patrick Cohen, Gautier Paux, Sylvaine Cartot‐Cotton, Maya Stefanova-Urena, Laure Deyme, Jihane Aouni, Bernard Sébastien, Aditya Bardia
Abstract
PURPOSE: AMEERA-5 investigated amcenestrant (oral selective estrogen receptor [ER] degrader) plus palbociclib versus letrozole plus palbociclib as first-line treatment for ER-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced/metastatic breast cancer (aBC). MATERIALS AND METHODS: In AMEERA-5 (ClinicalTrials.gov identifier: NCT04478266), a double-blind, double-dummy, international phase III trial, adult pre-/post-menopausal women and men without previous systemic therapy for ER+/HER2- aBC were randomly assigned 1:1 to amcenestrant 200 mg once daily + standard palbociclib dosage (125 mg once daily, 21 days on/7 days off) or letrozole 2.5 mg once daily + standard palbociclib dosage, stratified by de novo metastatic disease, postmenopausal women, and visceral metastasis. The primary end point was progression-free survival (PFS), compared using a stratified log-rank test with one-sided type I error rate of 2.5%. Secondary end points included overall survival (key secondary), pharmacokinetics, and safety. RESULTS: value = .9304); therefore, the study was stopped for futility. The 6-month PFS rate was 82.7% (95% CI, 79.0 to 85.8) with amcenestrant + palbociclib versus 86.9% (95% CI, 83.5 to 89.6) with letrozole + palbociclib. In the amcenestrant + palbociclib versus letrozole + palbociclib groups, treatment-emergent adverse events (any grade) occurred in 85.6% versus 85.4% of patients and grade ≥3 events in 46.3% versus 60.8%, respectively. CONCLUSION: The AMEERA-5 study was discontinued on the basis of the recommendation of the data monitoring committee at the interim futility analysis. No new safety signals were identified.