Chen Meiting, Huang Riqing, Rong Qixiang, Yang Wei, Shen Xiujiao, Sun Qi, Shu Ditian, Jiang Kuikui, Xue Cong, Peng Jing, An Xin, Li Haifeng, Xu Fei, Shi Yanxia
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
J Immunother Cancer. 2025 Apr 8;13(4):e011314. doi: 10.1136/jitc-2024-011314.
Optimal first-line therapy for metastatic triple-negative breast cancer (mTNBC) varied in different situations. This phase II trial explores the efficacy and safety of combination regimens with vacizumab, slelizumab and b-paclitaxel (BETINA) in first-line setting for mTNBC.
Patients with previously untreated advanced TNBC received tislelizumab 200 mg and bevacizumab on day 1 and nab-paclitaxel 125 mg/m on day 1, day 8 in 3-week cycles. Patients were randomized to bevacizumab 7.5 mg/kg or 15 mg/kg. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR2200058567).
30 female patients were enrolled from March 11, 2021 to February 5, 2024. Nine patients receiving bevacizumab 15 mg/kg experienced significantly higher hypertension rates versus 7.5 mg/kg (55.5% vs 0%), prompting subsequent enrollment of 12 additional patients at 7.5 mg/kg. By November 30, 2024, the ORR was 73.3% and the disease control rate was 90.0%, while the median PFS was 6.0 months and the median OS was 19.8 months. No new safety signal was reported. Common treatment-related adverse events (AEs) included peripheral sensory neuropathy (83.3%), dyspepsia (70.0%), anemia (70.0%), leukocytopenia (66.7%), and pruritus (53.3%). Hypothyroidism (30.0%) was the most frequent immune-related AE. Biomarker analysis indicated that lower baseline interleukin (IL)-1α was associated with poor survival, while IL-2, vascular endothelial growth factor-A and insulin-like growth factor binding protein-7 levels significantly decreased at progression. RNA sequencing highlighted the enrichment of the fatty acid metabolism pathway in poor responders.
BETINA study demonstrated promising efficacy and favorable tolerance in treating patients with mTNBC with bevacizumab with tislelizumab and nab-paclitaxel.
转移性三阴性乳腺癌（mTNBC）的最佳一线治疗方案在不同情况下有所不同。本II期试验探索了维西珠单抗、替雷利珠单抗和白蛋白结合型紫杉醇（BETINA）联合方案用于mTNBC一线治疗的疗效和安全性。
既往未接受过治疗的晚期TNBC患者在第1天接受替雷利珠单抗200mg和贝伐单抗治疗，并在第1天、第8天接受白蛋白结合型紫杉醇125mg/m²，每3周为一个周期。患者被随机分为接受7.5mg/kg或15mg/kg贝伐单抗治疗。主要终点是根据实体瘤疗效评价标准V.1.1由研究者评估的客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）和安全性。该试验已在中国临床试验注册中心注册（注册号：ChiCTR2200058567）。
2021年3月11日至2024年2月5日共纳入30名女性患者。接受15mg/kg贝伐单抗治疗的9名患者的高血压发生率显著高于接受7.5mg/kg治疗的患者（55.5%对0%），促使后续又有12名患者入组接受7.5mg/kg治疗。截至2024年11月30日，ORR为73.3%，疾病控制率为90.0%，中位PFS为6.0个月，中位OS为19.8个月。未报告新的安全信号。常见的治疗相关不良事件（AE）包括周围感觉神经病变（83.3%）、消化不良（70.0%）、贫血（70.0%）、白细胞减少（66.7%）和瘙痒（53.3%）。甲状腺功能减退（30.0%）是最常见的免疫相关AE。生物标志物分析表明，较低的基线白细胞介素（IL）-1α与较差的生存率相关，而在疾病进展时IL-2、血管内皮生长因子-A和胰岛素样生长因子结合蛋白-7水平显著降低。RNA测序突出显示了无反应者中脂肪酸代谢途径的富集。
BETINA研究表明，贝伐单抗联合替雷利珠单抗和白蛋白结合型紫杉醇治疗mTNBC患者具有良好的疗效和耐受性。
