低剂量阿帕替尼联合口服长春瑞滨治疗经治的HER2阴性转移性乳腺癌的疗效与安全性

The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

作者信息

Huang Jia-Yi, Chen Xue-Lian, Xie Xiao-Feng, Song Lin, Chen Li-Ping, Lan Xiao-Feng, Bai Xue, Chen Xiao, Du Cai-Wen

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, Guangdong, China.

出版信息

Cancer Med. 2024 Apr;13(8):e7181. doi: 10.1002/cam4.7181.

DOI:10.1002/cam4.7181

PMID:38659376

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11043681/

Abstract

BACKGROUND

Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC.

METHODS

This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS.

RESULTS

The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%).

CONCLUSION

Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

摘要

背景

阿帕替尼是一种口服小分子酪氨酸激酶抑制剂，可阻断血管内皮生长因子受体-2。口服长春瑞滨是长春瑞滨生物碱的半合成化疗药物。阿帕替尼和口服长春瑞滨已被证明对转移性乳腺癌（mBC）有效。目前，多项小样本临床试验探讨了阿帕替尼联合口服长春瑞滨治疗mBC的疗效。

方法

本回顾性研究纳入了100例人表皮生长因子受体2（HER2）阴性的mBC患者，这些患者在2017年2月至2023年3月期间接受低剂量阿帕替尼（每日口服250mg）联合口服长春瑞滨治疗，直至疾病进展或出现不耐受。采用SPSS 26.0软件和GraphPad Prism 8软件分析无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、临床获益率（CBR）、疾病控制率（DCR）及安全性。采用单因素和多因素Cox比例风险回归模型确定与PFS和OS显著相关的因素。

结果

本研究的中位随访时间为38.1个月。在100例HER2阴性的mBC患者中，66例为激素受体（HR）阳性/HER2阴性，34例为三阴性乳腺癌（TNBC）。中位PFS和OS分别为6.0个月（95%CI，5.2-6.8个月）和23.0个月（95%CI，19.9-26.1个月）。HR阳性/HER2阴性和TNBC亚组之间的PFS（p=0.239）和OS（p=0.762）无统计学差异。ORR、CBR和DCR分别为21.0%、58.0%和78.0%。95例患者（95.0%）发生了不同程度的不良事件（AE），38.0%的患者发生3-4级AE。我们观察到最常见的3-4级AE为中性粒细胞减少（30.0%）和白细胞减少（25.0%）。