Multinational phase 3 trial of abemaciclib plus fulvestrant for advanced breast cancer after progression on CDK4/6 inhibition

CDK4/6 inhibition combined with endocrine therapy is the standard first-line treatment for HR-positive, HER2-negative advanced breast cancer (aBC); however, disease progression occurs in almost all patients and additional treatment options are needed. The multinational phase 3 postMONARCH trial evaluated a switch in ET with or without CDK4/6 inhibition after disease progression on CDK4/6 inhibition plus aromatase inhibitor. Patients were randomized to abemaciclib plus fulvestrant or placebo plus fulvestrant. Primary end point was investigator-assessed progression-free survival. Median progression-free survival was 6.0 months with abemaciclib plus fulvestrant versus 5.3 months with placebo plus fulvestrant (HR 0.73; p=0.017). Among patients with measurable disease, investigator-assessed objective response rate was 17% versus 7% (p=0.015). There were no new safety signals. The authors conclude that abemaciclib plus fulvestrant significantly improved progression-free survival after disease progression on prior CDK4/6 inhibition plus endocrine therapy in patients with HR-positive, HER2-negative aBC, offering an additional targeted therapy option for these patients.