抗HER2治疗胆道肿瘤：疾病部位、HER2状态和生存结果的荟萃分析

IF 1.8 3区医学 Q3 ONCOLOGY

Oncology Pub Date : 2025-05-26 DOI:10.1159/000545308

Silvia Camera, Margherita Rimini, Silvia Foti, Federica Lo Prinzi, Francesco Vitiello, Elisabeth Amadeo, Mara Persano, Stefano Cascinu, Andrea Casadei-Gardini, Federico Rossari

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引用次数: 0

摘要

近年来，由于靶向治疗，转移性胆道癌（BTC）的治疗方案发生了深刻的变化。HER2是BTC中经常发生改变的一个有希望的分子靶标。目前的荟萃分析旨在描述her2阳性局部晚期/转移性BTC患者接受抗her2治疗的反应率和生存结果。此外，该研究旨在为HER2过表达BTC不断发展的治疗方案提供最新信息。方法：我们对文献进行了系统回顾，以确定研究包括HER2靶向治疗转移性BTC的任何方案的临床试验，并对二线II期试验进行了三项后续荟萃分析。第一个是比较HER2 - 3+组和HER2 - 2+组BTC患者的客观缓解率（ORR）。第二项研究根据肿瘤位置（胆囊癌[GBC]或肝外胆管癌[eCCA]与肝内胆管癌[iCCA]）比较患者的ORR。第三项研究评估了总生存期（OS）和无进展生存期（PFS）的总体结果。结果与HER2 2+相比，晚期BTC和HER2 3+患者的ORR更好，出现客观反应的概率高3.7倍（HR 3.70, 95% CI 1.34-10.25, p=0.0119）。同样，与iCCA患者相比，GBC或eCCA患者出现客观反应的可能性高出2.74倍（HR 2.74, 95% CI 1.12-6.73, p=0.0275）。二线或以上抗her2药物试验的加权汇总分析显示，mPFS为4.9个月（95% CI 4.2-5.6），而mOS为10.8个月（95% CI 9.0-12.8）。我们的荟萃分析显示，HER2 +转移性BTC患者和接受抗HER2治疗的GBC或eCCA患者的疗效得到改善，在II期试验分析的总体人群中有相当大的mPFS和mOS。进一步的研究对证实我们的初步结果至关重要。

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Anti-Human Epidermal Growth Factor Receptor-2 Therapies in Biliary Tract Cancers: A Meta-Analysis on Disease Location, Human Epidermal Growth Factor Receptor-2 Status, and Survival Outcomes.

Introduction: In recent years, the therapeutic scenario of metastatic biliary tract cancers (BTCs) beyond first-line has profoundly changed owing to target therapies. human epidermal growth factor receptor-2 (HER2) represents a promising molecular target that is frequently altered in BTC. The present meta-analyses aimed to describe the response rates and survival outcomes in patients with HER2-positive locally advanced/metastatic BTC treated with anti-HER2 therapies. Moreover, the study is intended to provide an update on the evolving therapeutic scenario of HER2-overexpressed BTC.

Methods: We performed a systematic review of the literature to identify clinical trials investigating any regimen comprising a HER2-targeted therapy for metastatic BTC, and we conducted three subsequent meta-analyses on second-line phase II trials. The first one was performed to compare the group of HER2 3+ versus the group of HER2 2+ BTC patients for objective response rate (ORR). The second one compared patients according to the tumor location (gallbladder carcinoma [GBC] or extrahepatic cholangiocarcinoma [eCCA] versus intrahepatic cholangiocarcinoma [iCCA]) for ORR. The third one evaluated the overall outcomes in terms of overall survival (OS) and progression-free survival (PFS).

Results: Patients with advanced BTC and HER2 3+ had better ORR compared to HER2 2+, with a 3.7-fold higher probability of experiencing objective responses (HR 3.70, 95% CI, 1.34-10.25, p = 0.0119). Likewise, patients with GBC or eCCA had a 2.74-fold higher probability of experiencing an objective response compared to patients with iCCA (HR 2.74, 95% CI, 1.12-6.73, p = 0.0275). The weighted pooled analysis of trials with anti-HER2 agents in second line or beyond revealed an mPFS of 4.9 months (95% CI, 4.2-5.6), while mOS was 10.8 months (95% CI, 9.0-12.8).

Conclusions: Our meta-analyses have revealed improved efficacy in patients with HER2 3+ metastatic BTC and in patients with GBC or eCCA treated with anti-HER2 therapies, with a considerable mPFS and mOS in the overall population of the phase II trials analyzed. Further studies are paramount to confirm our preliminary results.

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.