In an interim analysis of a Chinese phase III trial (FCN-437c-III201) reported in JAMA Oncology, Yuan et al found that the addition of the novel CDK4/6 inhibitor fovinaciclib to aromatase inhibitor therapy was associated with significant improvement in progression-free survival in the first-line treatment of patients with hormone receptor–positive, HER2-negative advanced breast cancer.
Study Details
In the multicenter double-blind trial, 417 women with no history of systemic therapy for advanced disease were randomly assigned between March 2022 and June 2023 to receive fovinaciclib at 200 mg once daily on days 1 to 21 (n = 208) or placebo (n = 209), both with letrozole at 2.5 mg or anastrozole at 1 mg once daily on days 1 to 28 in 28-day cycles. Patients had a median age of 57.0 years. Premenopausal or perimenopausal patients also received subcutaneous goserelin at 3.6 mg on day 1. The primary endpoint of the study was progression-free survival on blinded independent central review (BICR).
Key Findings
At the prespecified interim analysis at a median follow-up of 16.6 months (range = 0.3–27.8 months), median progression-free survival was not reached (95% confidence interval [CI] = not evaluable to not evaluable) in the fovinaciclib group vs 20.2 months (95% CI = 16.4 months to not evaluable) in the control group (hazard ratio [HR] = 0.55, 95% CI = 0.38–0.77, P < .001).
Overall survival data were not mature (9.6% maturity). The BICR-assessed objective response rate was 66.3% in the fovinaciclib group vs 39.2% in the control group, and median duration of response was not reached (95% CI = 20.3 months to not evaluable) vs 18.4 months (95% CI = 12.9 months to not evaluable).
Longitudinal changes in global health status, function domains, and symptom domains on the EORTC Quality of Life Questionnaire Core 30 were similar in the two groups.
Treatment-related grade 3 or higher adverse events occurred in 85.1% of the fovinaciclib group vs 14.4% of the control group; the most common in the fovinaciclib group were hematologic (decreased neutrophils in 76.4% and decreased white blood cells in 55.3%). Serious adverse events occurred in 14.4% vs 11.5% of patients. Treatment-related adverse events led to treatment discontinuation in two patients in each group.
The investigators concluded: “In this randomized clinical trial, adding fovinaciclib to first-line aromatase inhibitor conferred significant and clinically meaningful [progression-free survival] benefit and consistent improvements in other efficacy outcomes, along with manageable safety and unaffected quality of life.”
Binghe Xu, MD, PhD, of the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, is the corresponding author for the JAMA Oncology article.
DISCLOSURE: The study was supported by Avanc Pharmaceutical Co Ltd, National Natural Science Foundation of China, and others. For full disclosures of the study authors, visit jamanetwork.com.
