抗人表皮生长因子2制剂治疗胆管癌的安全性与有效性：一项系统评价
Safety and Efficacy of Anti-Human Epidermal Growth Factor 2 Agents in the Treatment of Biliary Tract Cancers: A Systematic Review.
作者信息
Naleid Nikolas, Pawar Omkar, Chakrabarti Sakti, Jin Zhaohui, Mangla Ankit, Mahipal Amit
机构信息
Department of Internal Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH.
Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH.
出版信息
JCO Precis Oncol. 2025 Apr;9:e2400594. doi: 10.1200/PO-24-00594. Epub 2025 Apr 16.
PURPOSE
Limited treatment options exist for patients with locally advanced or metastatic biliary tract cancers (BTCs). Recently, several clinical trials provided preliminary evidence for human epidermal growth factor receptor 2 (HER2) as a new target for patients with HER2-expressing BTC. We conducted a systematic review and pooled analysis of the safety and efficacy of anti-HER2 agents in patients with advanced BTCs.
METHODS
A comprehensive search of PubMed/MEDLINE and EMBASE was performed to identify phase I, II, or III clinical trials published between January 2019 and March 2024 that evaluated anti-HER2 therapy in locally advanced or metastatic BTC. Participant data included in the analysis were from trials evaluating the efficacy and safety of various anti-HER2 agents. The primary end points included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). The secondary end points included incidence of treatment-related adverse events (TRAEs), rate of treatment discontinuation, and death.
RESULTS
The analysis included 368 patients from eight publications diagnosed with advanced BTC. Patients were treated with several anti-HER2 agents including zanidatamab, pertuzumab plus trastuzumab, tucatinib plus trastuzumab, trastuzumab deruxtecan, trastuzumab plus chemotherapy, trastuzumab-pkrb plus chemotherapy, and neratinib. The pooled ORR and DCR were 34% (95% CI, 24 to 44) and 64% (95% CI, 51 to 77), respectively. The pooled weighted PFS and median overall survival were 4.8 and 9.4 months, respectively. The pooled duration of response for the reporting trials was 5.0 months. In the study cohort, 82.6% of patients experienced any adverse event and 32.1% experienced a grade 3-4 adverse event. Only 5.7% of the patients discontinued treatment secondary to TRAEs.
CONCLUSION
In patients with HER2-expressing BTCs, anti-HER2 therapies are viable options, particularly in the second-line setting.
目的
局部晚期或转移性胆管癌（BTC）患者的治疗选择有限。最近，多项临床试验为人类表皮生长因子受体2（HER2）作为HER2表达型BTC患者的新靶点提供了初步证据。我们对晚期BTC患者中抗HER2药物的安全性和疗效进行了系统评价和汇总分析。
方法
全面检索PubMed/MEDLINE和EMBASE，以确定2019年1月至2024年3月期间发表的评估局部晚期或转移性BTC抗HER2治疗的I、II或III期临床试验。纳入分析的参与者数据来自评估各种抗HER2药物疗效和安全性的试验。主要终点包括客观缓解率（ORR）、疾病控制率（DCR）和无进展生存期（PFS）。次要终点包括治疗相关不良事件（TRAE）的发生率、治疗中断率和死亡率。
结果
分析纳入了来自8篇文献的368例诊断为晚期BTC的患者。患者接受了多种抗HER2药物治疗，包括zanidatamab、帕妥珠单抗加曲妥珠单抗、图卡替尼加曲妥珠单抗、曲妥珠单抗德卢替康、曲妥珠单抗加化疗、曲妥珠单抗-pkrb加化疗和来那替尼。汇总的ORR和DCR分别为34%（95%CI，24至44）和64%（95%CI，51至77）。汇总的加权PFS和中位总生存期分别为4.8个月和9.4个月。报告试验的汇总缓解持续时间为5.0个月。在研究队列中，82.6%的患者发生了任何不良事件，32.1%的患者发生了3-4级不良事件。仅5.7%的患者因TRAE而中断治疗。
结论
对于HER2表达型BTC患者，抗HER2治疗是可行的选择，尤其是在二线治疗中。
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