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

This final analysis includes an additional 11-month follow-up.

本次最终分析包括了额外的11个月随访。

Background

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

评估双瑞西利联合氟维司群在激素受体阳性、ERBB2阴性晚期乳腺癌中的疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlledphase 3 randomized clinical trial was conducted at 64 hospitals in China between December 8, 2021, and October 24, 2022.

设计、环境和参与者：这项双盲、安慰剂对照的III期随机临床试验在中国的64家医院进行，从2021年12月8日至2022年10月24日。

Patients were enrolled and randomly assigned in a 2:1 to receive bireociclib plus fulvestrant or placebo plus fulvestrant.

患者被纳入并以2:1的比例随机分配接受bireociclib加fulvestrant或安慰剂加fulvestrant治疗。

Data were analyzed from April 2024 to December 2025.

数据分析从2024年4月持续到2025年12月。

Methods

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).

患者接受口服每12小时一次的瑞波西利360毫克，或安慰剂，与肌肉注射的氟维司群500毫克联合使用（第1个周期的第1天和第15天，随后每个28天周期的第1天）。

main_outcomes_and_measures

The primary end point was investigator-assessed progression-free survival(PFS).

主要终点是研究者评估的无进展生存期（PFS）。

Secondary end points included overall survival, objective response rate, duration of response, and safety.

次要终点包括总生存、客观缓解率、缓解持续时间以及安全性。

Results

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.

在纳入的305名患者中，平均（标准差）年龄为54.1（10.2）岁，数据截止时的中位（四分位数间距）随访时间为19（18.5-19.6）个月。

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.

患者被随机分配接受 bireociclib 加 fulvestrant (n = 204) 或安慰剂加 fulvestrant (n = 101)；275 名患者（90.2%）有可测量的疾病，268 名患者（87.9%）之前接受过全身化疗。

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).

bireociclib 加 fulvestrant 显著延长了无进展生存期（PFS），与安慰剂相比（中位 PFS，14.7 个月 [95% CI, 11.1-20.2] 对比 7.3 个月 [95% CI, 5.5-11.0]；风险比，0.54；95% CI, 0.40-0.74；P < .001）。

The objective response ratewas 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]).

在双瑞西利组中，客观缓解率更高（45.6% [95% 置信区间, 38.6-52.7] 对比 14.9% [95% 置信区间, 8.6-23.3]），且中位持续时间延长，与安慰剂相比（未达到 [95% 置信区间, 11.1 至未达到] 对比 13.1 个月 [95% 置信区间, 10.2 至未达到]）。

Safety was consistent with the interim findings and the profiles of known cyclin-dependent kinase 4/6 inhibitors.

安全性与中期发现一致，并与已知的细胞周期依赖性激酶4/6抑制剂的特征相符。

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.

在多个患者特征（如绝经状态、转移部位、既往治疗、无病间隔期、ESR1/PIK3CA/TP53突变等）的亚组分析中，与安慰剂相比，bireociclib显示出一致的无进展生存（PFS）改善。

Patients with early-onset diarrhea appeared to derive more benefit from bireociclib (hazard ratio, 0.49; 95% CI, 0.36-0.68).

早期出现腹泻的患者似乎从bireociclib中获益更多（风险比，0.49；95%置信区间，0.36-0.68）。

conclusions_and_relevance

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.

BRIGHT-2 随机临床试验的最终分析确认了在 fulvestrant 治疗基础上添加 bireociclib 可以改善 HR 阳性、ERBB2 阴性的 ABC 患者在先前内分泌治疗进展后的无进展生存期（PFS），且安全性可控，作为这些患者的治疗选择。

trial_registration

ClinicalTrials.gov Identifier: NCT05077449.

ClinicalTrials.gov 注册号：NCT05077449。