Efficacy and Safety of Dual Therapy with HER2-inhibitors (Pertuzumab and Trastuzumab) in Gastric or Gastroesophageal Tumors: A Systematic Review and Meta-analysis.

IF 1.6 Q4 ONCOLOGY

Journal of Gastrointestinal Cancer Pub Date : 2025-09-22 DOI:10.1007/s12029-025-01310-z

Geraldo Lucas Lopes Costa, João Victor Ramos da Cruz, José Roberto Alves, Saint Clair Vieira de Oliveira, Leticia Vieira Dos Santos Ribeiro, Arthur Henrique Gohr, Daniella Serafin Couto Vieira

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引用次数: 0

Abstract

Background: The benefit of adding dual HER2 inhibition with Pertuzumab (P) and Trastuzumab (T) to chemotherapy (cT) in HER2-positive gastric or gastroesophageal junction (GEJ) cancer is not yet fully elucidated.

Methods: A systematic search of PubMed, Cochrane Central, Embase, Web of Science, SciELO, and LILACS identified clinical trials investigating adjuvant or neoadjuvant regimens combining (P), (T) and (cT). Hazard ratios (HRs) and odds ratios (ORs) for binary endpoints were calculated, with 95% confidence intervals (CIs).

Results: Four clinical trials comprising a total of 1,225 patients were included. Dual HER2 blockade plus (cT) showed a significant benefit in survival analysis (HR 0.77, 95% CI 0.69-0.86), especially in terms of overall survival (HR 0.78, 95% CI 0.61-0.99) and progression-free survival (HR 0.73, 95% CI 0.62-0.85). Pathological response rates were higher compared with (cT) alone (OR 1.62, 95% CI 0.98-2.66). Treatment was associated with an increased overall adverse event rate (OR 1.48, 95% CI 1.32-1.66), particularly any-grade diarrhea, hypokalemia, fatigue, and pulmonary infection. Serious adverse events, including deaths and complications, were not significantly different (OR 0.87, 95% CI 0.51-1.49).

Conclusions: This systematic review and meta-analysis of clinical trials demonstrates that adding (P), (T) and (cT) improves survival and pathological response in HER2-positive gastric and GEJ tumors, with a manageable safety profile.

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her2抑制剂（帕妥珠单抗和曲妥珠单抗）双重治疗胃或胃食管肿瘤的疗效和安全性：一项系统评价和荟萃分析

背景：在HER2阳性胃或胃食管交界处（GEJ）癌的化疗（cT）中加入帕妥珠单抗(P)和曲妥珠单抗(T)双重HER2抑制的益处尚未完全阐明。方法：系统检索PubMed、Cochrane Central、Embase、Web of Science、SciELO和LILACS，确定了研究辅助或新辅助方案联合(P)、(T)和（cT）的临床试验。计算二元终点的风险比（hr）和优势比（ORs）， 95%置信区间（ci）。结果：纳入4项临床试验，共1225例患者。双HER2阻断+ (cT)在生存分析中显示出显著的益处（HR 0.77, 95% CI 0.69-0.86），特别是在总生存（HR 0.78, 95% CI 0.61-0.99）和无进展生存（HR 0.73, 95% CI 0.62-0.85）方面。病理反应率高于（cT）单独治疗（OR 1.62, 95% CI 0.98-2.66）。治疗与总体不良事件发生率增加相关（OR 1.48, 95% CI 1.32-1.66），特别是任何级别的腹泻、低钾血症、疲劳和肺部感染。严重不良事件，包括死亡和并发症，没有显著差异（OR 0.87, 95% CI 0.51-1.49）。结论：本临床试验的系统回顾和荟萃分析表明，在her2阳性的胃和GEJ肿瘤中，添加(P)、(T)和（cT）可改善生存和病理反应，并具有可控的安全性。

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

Journal of Gastrointestinal Cancer ONCOLOGY-

CiteScore

3.80

自引率

0.00%

发文量

121

期刊介绍： The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.