目前尚不清楚节拍化疗与免疫检查点阻断联合使用是否优于常规化疗。在这里，我们进行了节拍化疗联合 PD-1 阻断的 2 期临床试验，利用贝叶斯自适应随机化和疗效监测来比较传统化疗和 PD-1 阻断联合的疗效。符合条件的患者患有转移性 HER2 阴性乳腺癌，并且未接受过超过一种既往标准化疗。患者（总数 n = 97）被随机接受（1）节拍长春瑞滨 (NVB) 单药治疗（n = 11），（2）NVB 加抗 PD-1 特瑞普利单抗（n = 7），（3）抗血管生成贝伐珠单抗、NVB 和特瑞普利单抗 (n = 27)，(4) 传统顺铂、NVB 和特瑞普利单抗 (n = 26)，或 (5) 节拍环磷酰胺、卡培他滨、NVB 和特瑞普利单抗（VEX 队列）(n = 26)。主要终点是疾病控制率（DCR）。次要目标包括无进展生存期（PFS）和安全性。该研究达到了主要终点。 VEX (69.7%) 和顺铂 (73.7%) 队列的 DCR 最高。 VEX队列中患者的中位PFS最长，达到6.6个月，其次是贝伐单抗（4.0个月）和顺铂（3.5个月）队列。总的来说，五种治疗方案的耐受性良好，其中恶心和中性粒细胞减少是最常见的不良事件。探索性质谱流式分析表明节拍 VEX 化疗可重新编程全身免疫反应。总之，本研究的临床和转化数据表明，节拍性 VEX 化疗联合 PD-1 阻断可以成为乳腺癌患者的一种治疗选择。 ClinicalTrials.gov 标识符：NCT04389073 .© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

It remains unclear whether metronomic chemotherapy is superior to conventional chemotherapy when combined with immune checkpoint blockade. Here we performed a phase 2 clinical trial of metronomic chemotherapy combined with PD-1 blockade to compare the efficacy of combined conventional chemotherapy and PD-1 blockade using Bayesian adaptive randomization and efficacy monitoring. Eligible patients had metastatic HER2-negative breast cancer and had not received more than one prior line of standard chemotherapy. Patients (total n = 97) were randomized to receive (1) metronomic vinorelbine (NVB) monotherapy (n = 11), (2) NVB plus anti-PD-1 toripalimab (n = 7), (3) anti-angiogenic bevacizumab, NVB and toripalimab (n = 27), (4) conventional cisplatin, NVB and toripalimab (n = 26), or (5) metronomic cyclophosphamide, capecitabine, NVB and toripalimab (the VEX cohort) (n = 26). The primary endpoint was disease control rate (DCR). Secondary objectives included progression-free survival (PFS) and safety. The study met the primary endpoint. The VEX (69.7%) and cisplatin (73.7%) cohorts had the highest DCR. The median PFS of patients in the VEX cohort was the longest, reaching 6.6 months, followed by the bevacizumab (4.0 months) and cisplatin (3.5 months) cohorts. In general, the five regimens were well tolerated, with nausea and neutropenia being the most common adverse events. An exploratory mass cytometry analysis indicated that metronomic VEX chemotherapy reprograms the systemic immune response. Together, the clinical and translational data of this study indicate that metronomic VEX chemotherapy combined with PD-1 blockade can be a treatment option in patients with breast cancer. ClinicalTrials.gov Identifier: NCT04389073 .© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.