Multinational randomized phase 2 trial of 600- vs 400-mg first-line ribociclib for HR-positive HER2-negative advanced breast cancer

First-line ribocilib, 600 mg once daily showed substantial survival benefits in patients with HR-positive/HER2-negative advanced breast cancer (HR+ HER2- aBC) in the phase 3 MONALEESA trials but was associated with dose-dependent adverse events that were manageable with dose reduction. The multinational randomized phase 2 AMALEE trial compared ribociclib, 400 mg once daily versus ribociclib, 600 mg once daily. In the final analysis of this trial of 376 women with HR+ HER2- aBC, ribociclib, 400 mg did not meet noninferiority criteria vs ribociclib, 600 mg, for overall response rate (48,9% vs 56.1%). The response duration and progression-free survival were similar, while Fridericia-correcten QT interval prolongation and neutropenia rates were lower in the 400-mg group. The authors conclude that the ribociclib starting dose for HR+ HER2- aBC should remaine 600 mg, but dose reduction can help manage certain adverse events.