Dr Hu on the Evaluation of Tibremciclib Plus Fulvestrant in HR+/HER2– Advanced Breast Cancer

Xichun Hu, MD, PhD, professor, chief physician, doctoral supervisor, Fudan University, director, Department of Medical Oncology, Fudan University Shanghai Cancer Center, discusses the evaluation of tibremciclib (BPI-16350) plus fulvestrant (Faslodex) vs placebo plus fulvestrant in patients with hormone receptor–positive, HER2-negative advanced breast cancer following progression on prior endocrine therapy. This agent was evaluated in the randomized, multicenter, double-blind, phase 3 Tiffany trial (NCT05433480); interim results were shared at the 2024 ESMO Annual Congress.

The randomized, multicenter, double-blind study focuses on patients with hormone receptor–positive, HER2-negative advanced breast cancer who have progressed on prior endocrine therapy. Eligible patients (n = 274) were randomly assigned 2:1 to receive either tibremciclib at400 mg orally once daily plus fulvestrant at 500 mg intramuscularly (n = 184) or placebo plus fulvestrant (n = 90). The primary end point was investigator-assessed progression-free survival (PFS), and secondary end points included PFS per independent review committee, objective response rate, disease control rate, clinical benefit rate, duration of response, overall survival, and safety. The trial enrolled patients between May 2022 and April 2023 across 68 centers in China, with a data cutoff for interim analysis of August 31, 2023. The study aims to detect the ability of tibremciclib plus fulvestrant to prolong PFS vs placebo plus fulvestrant with 90% power. One interim analysis was performed with approximately 69% of PFS events occurring, and a final analysis was conducted after 100% of PFS events were recorded.

Tibremciclib is a CDK4/6 inhibitor structurally similar to abemaciclib (Verzenio) and has shown increased specificity in targeting CDK4/6 during clinical trials, Hu begins. In Tiffany, the median investigator-assessed PFS was 11.1 months with the tibremciclib combination (95% CI, 9.2-12.8) vs 5.5 months (95% CI, 4.2-7.4) with the placebo combination (HR, 0.31; 95% CI, 0.21-0.47; stratified log-rank P < .0001). These outcomes demonstrate both statistical significance and meaningful clinical benefits with the tibremciclib regimen vs fulvestrant alone, he reports. Regarding safety, grade 3 or higher treatment-emergent adverse effects (TEAEs) occurred in 38.0% of patients in the tibremciclib group, Hu says, adding that tibremciclib was associated with an acceptable profile. Common grade 3 or higher TEAEs in the tibremciclib arm were neutropenia (13%), anemia (9%), leukopenia (7%), and hypokalemia (7%), he concludes.