依瑞布林联合吡罗替尼治疗曲妥珠单抗耐药her2阳性晚期乳腺癌：单组多中心II期试验（EPIC试验）

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S547569

Ruoyang Li, Meiqi Wang, Xiangshun Kong, Jie Ma, Xiuheng Qi, Zhenchuan Song

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引用次数: 0

摘要

目的：本研究旨在评估依瑞布林联合吡罗替尼治疗晚期her2阳性乳腺癌患者并表现出曲妥珠单抗耐药的有效性和安全性。该亚组患者通常面临惨淡的临床预后和有限的指导可用于治疗决策。患者和方法：her2阳性转移性乳腺癌，ECOG 0-1，既往曲妥珠单抗/紫杉烷治疗的患者（N=30）接受每日口服吡洛替尼400 mg，静脉注射埃瑞布林1.4 mg/m²（1/8天，21天周期，6个周期），随后服用吡洛替尼直到进展/无法忍受的毒性。主要终点为无进展生存期（PFS）。结果：在2021年2月至2023年9月期间，30名患者入组研究，中位年龄为57岁。所有患者先前都接受过曲妥珠单抗和紫杉烷治疗。截至2025年4月14日，中位随访时间为26个月。18例患者出现疾病进展或死亡。中位无进展生存期（PFS）为13.47个月（95%可信区间[CI]， 8.17-16.27）， 12个月PFS率为61.7% （95% CI, 44.2%-86.0%）。12个月总生存率为75.3% （95% CI 66.2-84.4）。客观有效率为56.7%（17/30）。疾病控制率（DCR）为80.0%(24/30)，临床获益率（CBR）为73.3%（22/30）。中位总生存期未达到。发生率超过30%的任何级别不良事件（AE）为中性粒细胞减少（73.3%）、腹泻（70%）、恶心/呕吐（66.7%）、周围神经病变（63.3%）、AST/ALT升高（43.3%）、厌食（33.3%）。没有与治疗相关的死亡。结论：对于曲妥珠单抗耐药的her2阳性晚期乳腺癌患者，埃瑞布林和Pyrotinib联合治疗是一种可行的治疗选择。尽管抗her2疗法取得了进展，但需要进一步的研究来解决这一特定临床情况下的剩余挑战。

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Eribulin plus Pyrotinib in Trastuzumab-Resistant, HER2-Positive Advanced Breast Cancer: A Single-Arm, Multicenter Phase II Trial (EPIC Trial).

Purpose: This study aimed to assess the efficacy and safety of combining Eribulin with Pyrotinib in patients diagnosed with advanced HER2-positive breast cancer and exhibiting resistance to trastuzumab. This subgroup of patients typically faces a bleak clinical prognosis with limited guidance available for treatment decisions.

Patients and methods: Patients (N=30) with HER2-positive metastatic breast cancer, ECOG 0-1, and prior trastuzumab/taxane therapy received oral Pyrotinib 400 mg daily and intravenous Eribulin 1.4 mg/m² (days 1/8 of 21-day cycles for 6 cycles), followed by Pyrotinib until progression/intolerable toxicity. The primary endpoint was progression-free survival (PFS).

Results: Between February 2021 and September 2023, 30 patients were enrolled in the study, with a median age of 57 years. All patients had previously received treatment with trastuzumab and taxanes. As of April 14, 2025, the median follow-up duration was 26 months. 18 patients experienced disease progression or death. The median progression-free survival (PFS) was 13.47 months (95% confidence interval [CI], 8.17-16.27), with a 12-month PFS rate of 61.7% (95% CI, 44.2%-86.0%). 12-month overall survival (OS) rate of 75.3% (95% CI 66.2-84.4). The objective response rate was 56.7% (17/30). The disease control rate (DCR) reached 80.0% (24/30), while the clinical benefit rate (CBR) was 73.3% (22/30). The median overall survival was not reached. Any adverse event (AE) of any grade with an incidence of more than 30% was Neutropenia (73.3%), diarrhea (70%), nausea/vomiting (66.7%), Peripheral neuropathy (63.3%), AST/ALT increased (43.3%), Anorexia (33.3%). There were no treatment-related deaths.

Conclusion: The combination of Eribulin and Pyrotinib emerges as a viable treatment option for HER2-positive advanced breast cancer patients who have exhibited resistance to trastuzumab. Despite advancements in anti-HER2 therapies, further research is required to address remaining challenges in this specific clinical scenario.

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.