Multicenter phase 3 trial of fovinaciclib as first-line therapy for advanced HR-positive, HER2-negative breast cancer

Fovinaciclib is an oral selective CDK4/6 inhibitor which showed greater potency than ribociclib and blood-brain barrier penetration in preclinical studies. A phase 3 trial at 63 centers in China evaluated fovinaciclib with an aromatase inhibitor as first-line therapy for advanced HR-positive, HER2-negative breast cancer. Patients who had not received systemic therapy for advanced disease were randomized 1:1 to receive fovinaciclib (n=208) or placebo (n=209) added to first-line letrozole or anastrazole (premenopausal and perimenopausal patients also received goserelin). The primary endpoint was progression-free survival (PFS) per blinded independent central review (BIRC). At the prespecified interim analysis (median follow-up 16.6 months; range 0.3-27.8), BRIC-PFS was not reached in the fovinaciclib arm versus 20.2 months in the placebo arm (HR 0.55; p<0.01). Consistent PFS benefit was observed in most patient subgroups. Fovinaciclib was also favored across secondary efficacy endpoint. Overall survival data were immature. The most common treatment-emergent adverse events (TRAEs) were hematologic toxicities, none of which led to serious adverse events or discontinuations. Incidence of discontinuation due to TRAEs was only 1.4% in both arms. Longitudinal changes in global health status, function domains, and symptom domains of EORTC QLQ C30 were similar between the two arms. The authors conclude that adding fovinaciclib to first-line aromatase inhibitor conferred significant PFS benefit, with manageable safety and unaffected quality of life (visual abstract).