Trastuzumab in Combination with Capecitabine Plus Cisplatin for the Treatment of Advanced HER2-positive Gastric Cancer: A Systematic Review and Meta-Analysis

AIM The primary objective of this study was to comprehensively evaluate and compare the therapeutic efficacy of trastuzumab in combination with capecitabine plus cisplatin versus capecitabine plus cisplatin in the management of patients diagnosed with advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. By generating robust evidence-based medical data, this research aimed to facilitate clinical decision-making and ultimately improve treatment outcomes for this specific patient population. METHODS A comprehensive computerized search was conducted across multiple databases, including Cochrane Library, Web of Science, PubMed, Embase, CNKI, CBM, VIP, and Wanfang to identify domestic and foreign clinical randomized controlled trials (RCTs), investigating the efficacy of trastuzumab in combination with capecitabine plus cisplatin for the treatment of patients with advanced HER2-positive gastric cancer. The search encompassed articles published from the inception of the databases until July 1, 2022. Two reviewers independently conducted literature screening, extracting data, and assessing the risk of bias in the included studies. Subsequently, a meta-analysis was conducted using RevMan 5.4 software. RESULTS This meta-analysis comprised 12 studies involving a total of 1199 patients diagnosed with advanced HER2-positive gastric cancer. The results revealed that the experimental group exhibited significantly higher rates of total effectiveness (relative risk (RR) = 1.31, 95% confidence interval (CI): 1.22-1.42, P < 0.00001) and control (RR = 1.64, 95% CI: 1.42-1.90, P < 0.00001) compared to the control group. Moreover, the experimental group showed a significant increase in median survival time compared to the control group (mean difference (MD) = 2.95, 95% CI: 2.54-3.36, P < 0.00001). Additionally, the experimental group exhibited a significantly higher quality of life score (MD = 11.19, 95% CI: 9.57-12.81, P < 0.00001) and demonstrated improved prognosis in terms of carbohydrate antigen 19-9 (CA19-9) levels, with a lower recurrence rate (MD = -17.18, 95% CI: -18.02-16.34, P < 0.00001). The experimental group showed a decrease in the stage of gastric cancer based on carbohydrate antigen 72-4 (CA72-4) levels and a reduction in recurrence rate compared to the control group (MD = -12.70, 95% CI: -13.39-12.01, P < 0.00001). However, a significant heterogeneity was found in carcinoembryonic antigen (CEA) levels (P < 0.00001, I 2 = 99%). Upon controlling for heterogeneity, the experimental group demonstrated a significant improvement in efficacy and a reduction in the metastasis rate of gastric cancer compared to the control group (MD = -12.70, 95% CI: -13.39 to -12.01, P < 0.00001). Furthermore, the experimental group exhibited a notable enhancement in the therapeutic efficacy of vascular endothelial growth factor (VEGF) and a superior prognosis compared to the control group (MD = -10.67, 95% CI: -12.18 to -9.16, P < 0.00001). CONCLUSION Trastuzumab in combination with capecitabine plus cisplatin demonstrated notable advantages over capecitabine plus cisplatin in terms of total effectiveness rate, control rate, survival time, and median survival time. Additionally, significant improvements were found in tumor diagnostic indicators, including CA19-9, CA72-4, CEA, and VEGF. These findings suggest that trastuzumab in combination with capecitabine plus cisplatin can be a preferred first-line treatment option for advanced HER2-positive gastric cancer, accompanying by a promising therapeutic efficacy.