The SONIA trial (NCT03425838) is an investigator-initiated multicenter, randomized phase III study that evaluated whether the sequence of an aromatase inhibitor plus CDK 4/6 inhibitor in the first-line setting followed by fulvestrant in the second line is superior to the sequence of an aromatase inhibitor in the first line followed by the combination of fulvestrant plus CDK4/6 inhibitor in the second line in patients with advanced HR+ HER-negative BC previously untreated with systemic therapy for loco-regional recurrent or metastatic disease. The gene discussed is CDK4; the disease is metastatic neoplasm.