Multicenter phase 3 trial of early versus deferred use of CDK4/6 inhibitors for advanced breast cancer

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in combination with endocrine therapy improve the outcomes of patients with HR-positive, HER2-negative advanced breast cancer (aBC) and can be used early as first-line treatment or deferred to second-line treatment. Randomized data comparing the use of CDK4/6i in the first- and second-line setting are lacking. The multicenter phase 3 SONIA trial in The Netherlands randomized 1,050 patients who had not received previous therapy for aBC to receive CDK4/6i in the first- or second-line setting. All patients received the same endocrine therapy, consisting of an aromatase inhibitor for first-line treatment and fulvestrant for second-line treatment. The primary end point was defined as the time from randomization to disease progression after second-line treatment (PFS2). There was no statistically significant benefit for the use of CDK4/6i as a first-line compared with second-line treatment (median PFS2 31.0 versus 26.8 months, respectively; HR 0.87; p=0.10). The health-related quality of life was similar in both groups. First-line CDK4/6i use was associated with longer CDK4/6i treatment durationa and more grade >3 adverse events. The authors conclude that these data challenge the need for first-line use of a CDK4/6i in all patients.