First-line treatment with CDK4/6 inhibitors in hormone receptor-positive, HER2-negative advanced breast cancer did not improve overall survival (OS) compared with second-line treatment. Updated results of the SONIA randomized trial show that at a median follow-up of 58.5 months (95% CI, 57.0-60.9), there were 606 deaths (57.7% of patients). Median OS was 47.9 months (95% CI, 44.0-54.3) for first-line and 48.1 months (95% CI, 44.7-52.0) for second-line (HR 0.91; 95% CI, 0.77-1.07; P = 0.24).[5] The study included 1050 patients with a median age of 64 years, with 524 randomized to first-line and 526 to second-line.[5] First-line treatment increased treatment-related toxicity.[5] Post hoc analysis suggests a first-line OS advantage in premenopausal patients.[5]