Bireociclib Plus Fulvestrant in HR-Positive, HER2-Negative Advanced Breast Cancer

Clinical Summary:

• Design/Population: The phase 3 BRIGHT-2 trial randomized 305 patients with HR-positive, HER-negative advanced breast cancer to receive bireociclib plus fulvestrant or placebo plus fulvestrant after progression on endocrine therapy.
• Key Outcomes: Bireociclib significantly improved progression-free survival and response rates compared with placebo, with consistent benefit across subgroups. Safety was consistent with the known profile of CDK4/6 inhibitors.
• Clinical Relevance: Bireociclib plus fulvestrant represents a potential treatment option for patients with endocrine-resistant advanced breast cancer, offering improved disease control with manageable toxicity.

Final results from the phase 3 BRIGHT-2 trial demonstrate that bireociclib plus fulvestrant significantly improves progression-free survival (PFS) compared with fulvestrant alone among previously treated patients with HR-positive, HER2-negative advanced breast cancer. 

Interim results “demonstrated the efficacy of bireociclib plus fulvestrant in [HR)-positive, [HER2)-negative advanced breast cancer after endocrine therapy progression,” stated Jiayu Wang, MD, National Clinical Research Center for Cancer, Beijing, China, and coauthors. “This final analysis includes an additional 11-month follow-up.”

In this double-blind, placebo-controlled study,  305 patients who experienced disease progression on prior endocrine therapy were randomized 2:1 to receive either 360 mg of twice daily bireociclib (n = 204) or placebo (n = 101) plus fulvestrant (n = 101). The primary end point was PFS.  Key secondary end points included overall survival (OS), objective response rate (ORR), duration of response, and safety. 

 At a median follow-up of 19 months, median PFS was 14.7 months in the bireociclib arm and 7.3 months in the placebo arm   ( hazard ratio [HR], 0.54; 95% [confidence interval [CI], 0.40 to 0.74; P < .001). The ORR was 45.6% in the bireociclib arm and 14.9% in the placebo arm. Median duration of response was not reached in the bireociclib arm and 13.1 months in the placebo arm. Safety was consistent with prior findings and no new safety signals observed.

PFS benefit was consistent across subgroups, including those defined by menopausal status, metastatic burden, prior therapies, and genomic alterations such as ESR1, PIK3CA, and TP53. Patients who developed early-onset diarrhea appeared to derive greater benefit. 

“The final analysis of the BRIGHT-2 randomized clinical trial confirms improved PFS with the addition of bireociclib to fulvestrant, with manageable safety,” concluded Dr Wang et al. These results frame bireociclib plus fulvestrant “as a treatment option for patients with HR-positive, [HER]-negative [advanced breast cancer] with progression after prior endocrine therapy.”  

Source:

Wang J, Zhang Q, Li H, et al. Bireociclib plus fulvestrant in advanced breast cancer after endocrine progression. JAMA Oncol. Published online: March 19, 2026. doi:10.1001/jamaoncol.2026.0318