Bireociclib Plus Fulvestrant in Advanced Breast Cancer After Endocrine Progression: The BRIGHT-2 Phase 3 Randomized...

The BRIGHT-2 interim analysis demonstrated the efficacy of bireociclib plus fulvestrant in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (ERBB2; previously HER2)-negative advanced breast cancer (ABC) after endocrine therapy progression. This final analysis includes an additional 11-month follow-up.

To evaluate the efficacy and safety of bireociclib plus fulvestrant in HR-positive, ERBB2-negative ABC.

This double-blind, placebo-controlled phase 3 randomized clinical trial was conducted at 64 hospitals in China between December 8, 2021, and October 24, 2022. Patients were enrolled and randomly assigned in a 2:1 to receive bireociclib plus fulvestrant or placebo plus fulvestrant. Data were analyzed from April 2024 to December 2025.

Patients received bireociclib, 360 mg, or placebo orally every 12 hours in combination with fulvestrant, 500 mg, intramuscularly (days 1 and 15 of cycle 1, then day 1 of each 28-day cycle).

The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival, objective response rate, duration of response, and safety.

Of 305 included patients, the mean (SD) age was 54.1 (10.2) years, and the median (IQR) follow-up at data cutoff was 19 (18.5-19.6) months. Patients were randomized to bireociclib plus fulvestrant (n = 204) or placebo plus fulvestrant (n = 101); 275 (90.2%) had measurable disease and 268 (87.9%) had received prior systemic chemotherapy. Bireociclib plus fulvestrant significantly prolonged PFS vs placebo (median PFS, 14.7 months [95% CI, 11.1-20.2] vs 7.3 months [95% CI, 5.5-11.0]; hazard ratio, 0.54; 95% CI, 0.40-0.74; P < .001). The objective response rate was higher (45.6% [95% CI, 38.6-52.7] vs 14.9% [95% CI, 8.6-23.3]) in the bireociclib group, with a prolonged median duration compared with placebo (not reached [95% CI, 11.1 to not reached] vs 13.1 months [95% CI, 10.2 to not reached]). Safety was consistent with the interim findings and the profiles of known cyclin-dependent kinase 4/6 inhibitors. Subgroup analyses across multiple patient characteristics (menopausal status, metastatic sites, prior treatment, disease-free interval, ESR1/PIK3CA/TP53 alterations and others) showed consistent PFS improvements with bireociclib vs placebo. Patients with early-onset diarrhea appeared to derive more benefit from bireociclib (hazard ratio, 0.49; 95% CI, 0.36-0.68).

The final analysis of the BRIGHT-2 randomized clinical trial confirms improved PFS with the addition of bireociclib to fulvestrant, with manageable safety as a treatment option for patients with HR-positive, ERBB2-negative ABC with progression after prior endocrine therapy.

ClinicalTrials.gov Identifier: NCT05077449.