CT099: BRIGHT-2最终分析：bireociclib联合氟维司汀作为晚期HR+/ her2乳腺癌患者二线内分泌治疗的III期临床试验

IF 12.5 1区医学 Q1 ONCOLOGY

Cancer research Pub Date : 2025-04-25 DOI:10.1158/1538-7445.am2025-ct099

Jiayu Wang, Qingyuan Zhang, Huiping Li, Zhongsheng Tong, Quchang Ouyang, Huihui Li, Yuee Teng, Biyun Wang, Tao Sun, Jingfen Wang, Wei Li, Zhaofeng Niu, Hongsheng Li, Chang Gong, Li Wang, Fei Liu, Xianghui Duan, Qiuli Wang, Binghe Xu

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Method: Eligible pts with HR+/HER2- ABC who have progressed on or after previous endocrine therapy were randomized 2:1 to receive bireociclib (360 mg po bid) or placebo with fulvestrant (500 mg im, d1, d15 for cycle1, d1 for the subquent cycles) on each 28-day cycle. Pts were stratified by endocrine resistance (primary vs secondary) and visceral metastases (yes vs no). The primary endpoint was investigator-assessed PFS per RECIST v1.1. A post hoc analysis was conducted to assess the impact of protocol-allowed dose reductions (120 mg decrements) on PFS in bireociclib plus fulvestrant (BF) group. Results: 305 eligible female pts were enrolled to receive BF (n = 204) or placebo plus fulvestrant (F, n = 101). 209 (68.5%) pts had visceral metastases, 78 (25.6%) pts with primary endocrine resistance and 73 (23.9%) pts had received chemotherapy for advanced disease. At data cutoff (Feb. 22, 2024), with a median follow-up of 18.99 months (mo), the investigator-assessed stratified median PFS (mPFS) was 14.69 mo (95% CI, 11.07-20.21) in BF group vs 7.33 mo (95% CI, 5.49-11.04) in F group (HR, 0.542; 95% CI, 0.399-0.735; p&lt;0.0001). The mPFS assessed by blinded independent central review (BICR) was 17.51 mo (95% CI, 13.83-23.06) in BF group vs 7.29 mo (95% CI, 5.49-9.46) in F group (HR, 0.462; 95% CI, 0.333-0.642; p&lt;0.0001). Improvement in PFS with BF treatment was consistent across all prespecified subgroups. HR for pts with bone-only metastases was 0.184; 95% CI, 0.063-0.541. For pts who didn't receive chemotherapy in advanced disease, the mPFS for the BF group and F group were 17.28 mo and 7.69 mo, respectively (HR, 0.559; 95% CI, 0.387-0.807). The overall survival data was yet immature, with a trend of survival benefit in BF group (HR, 0.762; 95% CI, 0.476-1.218; p=0.5221). The most common treatment-emergent adverse events (TEAEs) were hematologic toxicity and diarrhea and comparable to previously reported profiles. No new safety signal was observed. 86 pts (42.2%) received bireociclib dose reduction due to TEAEs in BF group. The mPFS was 14.52 mo (95% CI, 11.07 to NR) vs 14.75 mo (95% CI, 10.87 to NR) for pts with or without bireociclib dose reduction respectively, p=0.5758. Conclusions: Bireociclib plus fulvestrant exhibited superior efficacy and manageable tolerability as second-line endocrine therapy for HR+/HER2- ABC after prolonged follow-up, with benefits across different subgroups and clinically appropriate dose reductions not compromising efficacy. Citation Format: Jiayu Wang, Qingyuan Zhang, Huiping Li, Zhongsheng Tong, Quchang Ouyang, Huihui Li, Yuee Teng, Biyun Wang, Tao Sun, Jingfen Wang, Wei Li, Zhaofeng Niu, Hongsheng Li, Chang Gong, Li Wang, Fei Liu, Xianghui Duan, Qiuli Wang, Binghe Xu. 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引用次数: 0

摘要

背景：在light -2 （NCT05077449）中期分析中，bireociclib（一种新型选择性CDK4/6抑制剂）联合氟维西汀作为HR+/HER2-晚期乳腺癌（ABC）患者（pts）的二线治疗，显著提高了无进展生存期（PFS），具有可耐受的安全性。在此，我们报告11个月的额外随访后的最终分析。方法：符合条件的HR+/HER2- ABC患者在先前的内分泌治疗中或之后进展，随机分为2:1，每28天一个周期接受bireociclib （360 mg / bid）或安慰剂加氟维司汀（500 mg / im, d1， d15为第1周期，d1为后续周期）。根据内分泌抵抗（原发性与继发性）和内脏转移（有或没有）对患者进行分层。主要终点是研究者根据RECIST v1.1评估的PFS。进行了事后分析，以评估方案允许的剂量减少（减少120 mg）对bireociclib + fulvestrant （BF）组PFS的影响。结果：305名符合条件的女性患者入组接受BF （n = 204）或安慰剂加氟维司汀（F, n = 101）。209例（68.5%）PTS有内脏转移，78例（25.6%）PTS有原发性内分泌抵抗，73例（23.9%）PTS因疾病晚期接受化疗。截至数据截止日期（2024年2月22日），中位随访时间为18.99个月，研究者评估的BF组分层中位PFS （mPFS）为14.69个月（95% CI, 11.07-20.21）， F组为7.33个月（95% CI, 5.49-11.04） (HR, 0.542；95% ci, 0.399-0.735；p&肝移植;0.0001)。BF组mPFS为17.51个月（95% CI, 13.83-23.06）， F组mPFS为7.29个月（95% CI, 5.49-9.46） (HR, 0.462；95% ci, 0.333-0.642；p&肝移植;0.0001)。在所有预先指定的亚组中，BF治疗对PFS的改善是一致的。仅骨转移的患者HR为0.184；95% ci, 0.063-0.541。对于晚期疾病未接受化疗的患者，BF组和F组的mPFS分别为17.28个月和7.69个月(HR, 0.559；95% ci, 0.387-0.807)。总体生存数据尚不成熟，BF组有生存获益趋势(HR, 0.762；95% ci, 0.476-1.218；p = 0.5221)。最常见的治疗不良事件（teae）是血液学毒性和腹泻，与先前报道的情况相当。未观察到新的安全信号。BF组有86例（42.2%）患者因teae而接受降药治疗。两组患者的mPFS分别为14.52个月（95% CI, 11.07 - NR）和14.75个月（95% CI, 10.87 - NR）， p=0.5758。结论：经长期随访，Bireociclib + fulvestrant作为HR+/HER2- ABC的二线内分泌治疗显示出优越的疗效和可控的耐受性，不同亚组的获益和临床适当的剂量减少不会影响疗效。引用格式：王佳玉、张庆元、李惠萍、童忠生、欧阳曲昌、李慧慧、滕月娥、王碧云、孙涛、王景芬、李伟、牛兆峰、李宏生、龚畅、王莉、刘飞、段祥辉、王秋莉、徐炳和BRIGHT-2最终分析：bireociclib联合氟维司汀作为晚期HR+/ her2乳腺癌患者二线内分泌治疗的III期临床试验[摘要]。摘自：《2025年美国癌症研究协会年会论文集》；第二部分（最新进展，临床试验，并邀请s）；2025年4月25日至30日；费城（PA）： AACR；中国癌症杂志，2015;35(5):391 - 391。

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Abstract CT099: BRIGHT-2 final analysis: A phase III trial of bireociclib plus fulvestrant as second-line endocrine therapy for patients with advanced HR+/HER2-breast cancer

Background: At the BRIGHT-2 (NCT05077449) interim analysis, bireociclib (a novel selective CDK4/6 inhibitor) plus fulvestrant significantly improved progression-free survival (PFS) with a tolerable safety profile as second-line therapy for HR+/HER2- advanced breast cancer (ABC) patients (pts). Herein, we report the final analysis after 11-month of additional follow-up. Method: Eligible pts with HR+/HER2- ABC who have progressed on or after previous endocrine therapy were randomized 2:1 to receive bireociclib (360 mg po bid) or placebo with fulvestrant (500 mg im, d1, d15 for cycle1, d1 for the subquent cycles) on each 28-day cycle. Pts were stratified by endocrine resistance (primary vs secondary) and visceral metastases (yes vs no). The primary endpoint was investigator-assessed PFS per RECIST v1.1. A post hoc analysis was conducted to assess the impact of protocol-allowed dose reductions (120 mg decrements) on PFS in bireociclib plus fulvestrant (BF) group. Results: 305 eligible female pts were enrolled to receive BF (n = 204) or placebo plus fulvestrant (F, n = 101). 209 (68.5%) pts had visceral metastases, 78 (25.6%) pts with primary endocrine resistance and 73 (23.9%) pts had received chemotherapy for advanced disease. At data cutoff (Feb. 22, 2024), with a median follow-up of 18.99 months (mo), the investigator-assessed stratified median PFS (mPFS) was 14.69 mo (95% CI, 11.07-20.21) in BF group vs 7.33 mo (95% CI, 5.49-11.04) in F group (HR, 0.542; 95% CI, 0.399-0.735; p<0.0001). The mPFS assessed by blinded independent central review (BICR) was 17.51 mo (95% CI, 13.83-23.06) in BF group vs 7.29 mo (95% CI, 5.49-9.46) in F group (HR, 0.462; 95% CI, 0.333-0.642; p<0.0001). Improvement in PFS with BF treatment was consistent across all prespecified subgroups. HR for pts with bone-only metastases was 0.184; 95% CI, 0.063-0.541. For pts who didn't receive chemotherapy in advanced disease, the mPFS for the BF group and F group were 17.28 mo and 7.69 mo, respectively (HR, 0.559; 95% CI, 0.387-0.807). The overall survival data was yet immature, with a trend of survival benefit in BF group (HR, 0.762; 95% CI, 0.476-1.218; p=0.5221). The most common treatment-emergent adverse events (TEAEs) were hematologic toxicity and diarrhea and comparable to previously reported profiles. No new safety signal was observed. 86 pts (42.2%) received bireociclib dose reduction due to TEAEs in BF group. The mPFS was 14.52 mo (95% CI, 11.07 to NR) vs 14.75 mo (95% CI, 10.87 to NR) for pts with or without bireociclib dose reduction respectively, p=0.5758. Conclusions: Bireociclib plus fulvestrant exhibited superior efficacy and manageable tolerability as second-line endocrine therapy for HR+/HER2- ABC after prolonged follow-up, with benefits across different subgroups and clinically appropriate dose reductions not compromising efficacy. Citation Format: Jiayu Wang, Qingyuan Zhang, Huiping Li, Zhongsheng Tong, Quchang Ouyang, Huihui Li, Yuee Teng, Biyun Wang, Tao Sun, Jingfen Wang, Wei Li, Zhaofeng Niu, Hongsheng Li, Chang Gong, Li Wang, Fei Liu, Xianghui Duan, Qiuli Wang, Binghe Xu. BRIGHT-2 final analysis: A phase III trial of bireociclib plus fulvestrant as second-line endocrine therapy for patients with advanced HR+/HER2-breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited s); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2): nr CT099.

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来源期刊

Cancer research 医学-肿瘤学

CiteScore

16.10

自引率

0.90%

发文量

7677

审稿时长

2.5 months

期刊介绍： Cancer Research, published by the American Association for Cancer Research (AACR), is a journal that focuses on impactful original studies, reviews, and opinion pieces relevant to the broad cancer research community. Manuscripts that present conceptual or technological advances leading to insights into cancer biology are particularly sought after. The journal also places emphasis on convergence science, which involves bridging multiple distinct areas of cancer research. With primary subsections including Cancer Biology, Cancer Immunology, Cancer Metabolism and Molecular Mechanisms, Translational Cancer Biology, Cancer Landscapes, and Convergence Science, Cancer Research has a comprehensive scope. It is published twice a month and has one volume per year, with a print ISSN of 0008-5472 and an online ISSN of 1538-7445. Cancer Research is abstracted and/or indexed in various databases and platforms, including BIOSIS Previews (R) Database, MEDLINE, Current Contents/Life Sciences, Current Contents/Clinical Medicine, Science Citation Index, Scopus, and Web of Science.