Fovinaciclib Plus Endocrine Therapy Improves Progression-Free Survival in HR-Positive, HER2-Negative Advanced Breast Cancer

‌Clinical Summary:

• Design/Population: This phase 3 trial evaluated fovinaciclib plus letrozole or anastrozole versus placebo plus endocrine therapy as first-line treatment in patients with HR-positive, HER2-negative advanced breast cancer.
• Key Outcomes: Fovinaciclib significantly improved progression-free survival compared with endocrine therapy alone and demonstrated consistent benefit across secondary efficacy end points. The combination maintained a manageable safety profile and preserved quality of life.
• Clinical Relevance: These findings support fovinaciclib plus an aromatase inhibitor as a potential first-line treatment option in this setting. 

Results from a phase 3 trial demonstrated that fovinaciclib plus letrozole or anastrozole significantly improved progression-free survival (PFS) compared with endocrine therapy alone in patients with HR-positive, HER2-negative advanced breast cancer, supporting the combination as a potential first-line treatment option.

In this double-blind trial, 417 patients with HR-positive, HER2-negative advanced breast cancer who had not received prior systemic therapy for advanced disease were randomized 1:1 to receive either 200 mg of fovinaciclib (n = 208) or placebo (n = 209) once daily on days 1 through 21 of each 28-day cycle in combination with either 2.5 mg of  letrozole or 1 mg of anastrozole. Premenopausal or perimenopausal patients also received goserelin. 

The primary end point was PFS, assessed via blinded independent central review. Secondary end points included additional efficacy outcomes and safety, while overall survival (OS) and quality of life were exploratory end points.

At the prespecified interim analysis, with a median follow-up was 16.6 months, median PFS was not reached in the fovinaciclib arm compared with 20.2 months in the placebo arm (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.38 to 0.77; P < .001). The PFS benefit with fovinaciclib was generally consistent across most patient subgroups. 

Fovinaciclib also demonstrated favorable results across secondary efficacy end points. OS data remained immature, with only 40 events (9.6%) reported at the time of analysis.

The most common treatment-emergent adverse events were hematologic toxicities, none of which led to serious adverse events or permanent study drug discontinuation. Treatment discontinuation due to treatment-emergent adverse events occurred in 1.4% of patients in both treatment arms. 

Patient-reported quality of life outcomes, including global health status, functional domains, and symptom domains assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, remained similar between the treatment groups throughout the study. 

As study authors concluded, “adding fovinaciclib to first-line aromatase inhibitor conferred significant and clinically meaningful PFS benefit and consistent improvements in other efficacy outcomes, along with manageable safety and unaffected quality of life.” 

Source:

Yuan P, Liu Y, Li W, et al. Fovinaciclib for first-line therapy of advanced breast cancer: A randomized clinical trial. JAMA Oncol. Published online: June 1, 2026. doi: 10.1001/jamaoncol.2026.1938