breast cancer, locally advanced and metastatic First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC)

Abstract

Background: Endocrine therapy (ET) is an established first-line treatment for ABC. However, ET resistance and disease progression eventually occur in most patients. Cyclin-dependent kinase (CDK) 4/6 inhibition is a valid treatment strategy for HR+ ABC and may help overcome or delay ET resistance. Here we report interim results from MONALEESA-2 (NCT01958021), a double-blind, randomized, phase 3 trial evaluating the efficacy and safety of first-line ribociclib (a selective CDK4/6 inhibitor) + letrozole in women with HR + , HER2- ABC. Methods: Postmenopausal women (N = 668) with HR + , HER2- ABC with no prior systemic treatment for ABC were randomized (1:1) to receive ribociclib (600 mg/ day, 3-weeks-on/1-week-off ) + letrozole (2.5 mg/day, continuous) or placebo + letrozole. The primary endpoint was locally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS; key secondary endpoint), overall response rate (ORR), clinical benefit rate (CBR), and safety. A pre-planned interim analysis was conducted after 243 PFS events (information fraction 80%) had occurred. Results: Baseline patient characteristics were balanced between treatment arms. The study met its primary objective: at the interim analysis (data cut-off Jan 29, 2016), PFS was significantly improved in the ribociclib arm, with a hazard ratio of 0.556 (95% CI: 0.429-0.720; p = 0.00000329). Median PFS was not reached in the ribociclib arm (95% CI: 19.3-not estimable) vs 14.7 months in the placebo arm (95% CI: 13.0-16.5). In patients with measurable disease at baseline, ORR was 53% vs 37% (ribociclib vs placebo arm; p = 0.00028) and CBR was 80% vs 72% (p = 0.02). Common Grade 3/4 adverse events (>=5% of patients; ribociclib vs placebo arm) were neutropenia (59% vs 1%), leukopenia (21% vs 1%), hypertension (10% vs 11%), elevated alanine aminotransferase (9% vs 1%), lymphopenia (7% vs 1%), and elevated aspartate aminotransferase (6% vs 1%). OS data were immature at data cut-off. Conclusions: Ribociclib + letrozole was well tolerated and significantly prolonged PFS vs letrozole alone in postmenopausal women with HR + , HER2- ABC who had received no prior therapy for ABC.