Ribociclib + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative advanced breast cancer (ABC) who received no prior therapy for advanced disease

Introduction: Ribociclib, a selective, small-molecule inhibitor of CDK4/6, has exhibited antitumor activity as part of doublet or triplet therapy (ribociclib+ET ± PI3K-inhibitor or everolimus) in estrogen receptor-positive breast cancer models, and in the clinical setting. The phase 3, randomized, double-blind, international, MONALEESA-2 study is evaluating the efficacy and safety of ribociclib + letrozole vs. placebo + letrozole in patients with HR+, HER2-negative ABC who have received no prior systemic therapy for advanced disease. Methods: Postmenopausal women (N = 668) with confirmed HR+, HER2-negative ABC with measurable disease or ≥1 predominantly lytic bone lesion, ECOG-PS ≤1, and adequate bone marrow and organ function were enrolled. No prior systemic therapy for ABC or prior CDK4/6-inhibitor treatment were allowed; (neo)adjuvant therapy was allowed, if disease free interval was > 12 months after non-steroidal aromatase inhibitor treatment. Patients were randomized 1:1 to receive ribociclib (600 mg/day on Days 1 – 21 of each 28-day cycle) + letrozole (2.5 mg/day continuously) or placebo + letrozole, stratified by the presence of liver and/or lung metastases. Primary endpoint is PFS by local radiological assessment. The key secondary endpoint is OS; other secondary endpoints include ORR, CBR, and safety. Expected results: IDMC decided that the trial met its primary endpoint, significantly extending PFS compared to letrozole alone, at the pre-planned interim analysis. Data from the interim efficacy analysis, including PFS and supportive secondary endpoints, will be presented. Expected conclusions: Ribociclib + letrozole significantly improved PFS vs. letrozole monotherapy in postmenopausal women with HR+, HER2-negative ABC who had received no prior therapy for advanced disease.