Ribociclib, a selective CDK4/6 inhibitor, was evaluated in a phase 3 trial as first-line therapy for HR-positive, HER2-negative advanced breast cancer. The study involved 668 postmenopausal women who had not received prior systemic therapy. Patients were randomly assigned to receive ribociclib plus letrozole or placebo plus letrozole. The primary endpoint was progression-free survival (PFS), with a hazard ratio of 0.56 (95% CI, 0.43 to 0.72; P=3.29×10⁻⁶) indicating significantly longer PFS in the ribociclib group. After 18 months, PFS rates were 63.0% in the ribociclib group versus 42.2% in the placebo group. The overall response rate was 52.7% in the ribociclib group versus 37.1% in the placebo group. Common adverse events included neutropenia (59.3% in ribociclib group) and leukopenia (21.0% in ribociclib group), with 7.5% and 2.1% of patients discontinuing treatment due to adverse events, respectively. Ribociclib plus letrozole showed significant improvement in PFS and overall response rate compared to placebo plus letrozole. The trial was supported by Novartis Pharmaceuticals. The results suggest that ribociclib plus letrozole is a more effective first-line treatment for HR-positive, HER2-negative advanced breast cancer, although it is associated with higher myelosuppression.Ribociclib, a selective CDK4/6 inhibitor, was evaluated in a phase 3 trial as first-line therapy for HR-positive, HER2-negative advanced breast cancer. The study involved 668 postmenopausal women who had not received prior systemic therapy. Patients were randomly assigned to receive ribociclib plus letrozole or placebo plus letrozole. The primary endpoint was progression-free survival (PFS), with a hazard ratio of 0.56 (95% CI, 0.43 to 0.72; P=3.29×10⁻⁶) indicating significantly longer PFS in the ribociclib group. After 18 months, PFS rates were 63.0% in the ribociclib group versus 42.2% in the placebo group. The overall response rate was 52.7% in the ribociclib group versus 37.1% in the placebo group. Common adverse events included neutropenia (59.3% in ribociclib group) and leukopenia (21.0% in ribociclib group), with 7.5% and 2.1% of patients discontinuing treatment due to adverse events, respectively. Ribociclib plus letrozole showed significant improvement in PFS and overall response rate compared to placebo plus letrozole. The trial was supported by Novartis Pharmaceuticals. The results suggest that ribociclib plus letrozole is a more effective first-line treatment for HR-positive, HER2-negative advanced breast cancer, although it is associated with higher myelosuppression.