Efficacy, safety and exploratory analysis of neoadjuvant tislelizumab (a PD-1 inhibitor) plus nab-paclitaxel followed by epirubicin/cyclophosphamide for triple-negative breast cancer: a phase 2 TREND trial.

IF 40.8 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Signal Transduction and Targeted Therapy Pub Date : 2025-05-26 DOI:10.1038/s41392-025-02254-3

Qiang Zhang,Mozhi Wang,Yumeng Li,Hengjun Zhang,Yusong Wang,Xiuyun Chen,Litong Yao,Mingke Cui,Haoran Dong,Xiang Li,Jian Liu,Bo Zhu,Yingying Xu

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Abstract

The optimal chemotherapy backbone and specific population of triple-negative breast cancer (TNBC) patients that benefit from neoadjuvant immunotherapy are not well established. This prospective, single-arm, phase II TREND trial assessed the efficacy and safety of tislelizumab plus nab-paclitaxel and epirubicin/cyclophosphamide-based chemotherapy as a neoadjuvant treatment for TNBC (ChiCTR2000035262). The primary endpoint was pathological complete response (pCR), with the secondary endpoints including safety assessment and objective response rate (ORR). ScRNA-seq, bulk RNA-seq, TCR-seq, cyTOF and WES were performed on pre-treatment and post-treatment samples. Among 53 total enrolled patients, 44 completed the combined neoadjuvant therapy, and 30 of 44 patients (68.18%) achieved pCR. Additionally, 14 out of 44 patients had a complete response (31.82%), with an ORR of 93.18%. The most commonly observed treatment-related adverse events (TRAEs) were alopecia, nausea and liver injury with 6 cases classified as grade 3 or higher adverse events. Immune response-related pathways, including TNF signaling pathway, T cell receptor signaling pathway, were enriched in pCR group. Pre-treatment model was identified and construct to predict response to immunotherapy. CDKN1A+ CD8 T lymphocytes were enriched in pCR group after neoadjuvant immunotherapy. Dynamic change of immune-related pathways at an early stage during the neoadjuvant immunotherapy may be associated with the treatment efficacy. In conclusion, neoadjuvant treatment of tislelizumab with nab-paclitaxel and anthracycline-based chemotherapy showed promising clinical activity and was well-tolerated among TNBC patients, without high incidence of TRAEs. These findings provide evidence supporting neoadjuvant tislelizumab with chemotherapy as an effective rational approach for treating TNBC.

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新辅助tislelizumab（一种PD-1抑制剂）联合nab-紫杉醇联合表柔比星/环磷酰胺治疗三阴性乳腺癌的疗效、安全性和探索性分析：一项2期TREND试验。

从新辅助免疫治疗中获益的三阴性乳腺癌（TNBC）患者的最佳化疗骨干和特定人群尚未得到很好的确定。这项前瞻性单组II期TREND试验评估了tislelizumab联合nab-紫杉醇和表柔比星/环磷酰胺化疗作为TNBC新辅助治疗的有效性和安全性（ChiCTR2000035262）。主要终点是病理完全缓解（pCR），次要终点包括安全性评估和客观缓解率（ORR）。对处理前后样品进行ScRNA-seq、bulk RNA-seq、TCR-seq、cyTOF和WES检测。在53例入组患者中，44例完成了联合新辅助治疗，其中30例（68.18%）达到pCR。此外，44例患者中有14例完全缓解（31.82%），ORR为93.18%。最常见的治疗相关不良事件（TRAEs）为脱发、恶心和肝损伤，其中6例为3级或以上不良事件。pCR组免疫应答相关通路，包括TNF信号通路、T细胞受体信号通路富集。确定并构建治疗前模型以预测免疫治疗的反应。新辅助免疫治疗后，pCR组CDKN1A+ CD8 T淋巴细胞富集。新辅助免疫治疗早期免疫相关通路的动态变化可能与治疗效果有关。综上所述，新辅助治疗tislelizumab联合nab-紫杉醇和蒽环类化疗显示出良好的临床活性，并且在TNBC患者中耐受性良好，没有高发生率的trae。这些发现为新辅助tislelizumab联合化疗作为治疗TNBC有效合理的方法提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

44.50

自引率

1.50%

发文量

384

审稿时长

5 weeks

期刊介绍： Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.