This randomized, placebo-controlled, phase 3 trial evaluated the efficacy and safety of ribociclib combined with letrozole as first-line treatment for postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer who had not received previous systemic therapy. The primary endpoint was investigator-assessed progression-free survival. Patients were randomly assigned to receive either ribociclib (600 mg/day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg/day) or placebo plus letrozole. The median duration of progression-free survival was significantly longer in the ribociclib group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10⁻⁶) compared to the placebo group. The overall response rate was higher in the ribociclib group (52.7% vs. 37.1%), and the clinical benefit rate was also higher (80.1% vs. 71.8%). Common grade 3 or 4 adverse events included neutropenia and leukopenia. The study concluded that ribociclib plus letrozole significantly prolonged progression-free survival and improved overall response rates compared to placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group.This randomized, placebo-controlled, phase 3 trial evaluated the efficacy and safety of ribociclib combined with letrozole as first-line treatment for postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer who had not received previous systemic therapy. The primary endpoint was investigator-assessed progression-free survival. Patients were randomly assigned to receive either ribociclib (600 mg/day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg/day) or placebo plus letrozole. The median duration of progression-free survival was significantly longer in the ribociclib group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10⁻⁶) compared to the placebo group. The overall response rate was higher in the ribociclib group (52.7% vs. 37.1%), and the clinical benefit rate was also higher (80.1% vs. 71.8%). Common grade 3 or 4 adverse events included neutropenia and leukopenia. The study concluded that ribociclib plus letrozole significantly prolonged progression-free survival and improved overall response rates compared to placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group.