Efficacy and safety of anti-CLDN18.2 therapies in advanced or metastatic gastric, gastro-oesophageal junction, and oesophageal carcinomas with CLDN18.2 positivity: a systematic review and meta-analysis.
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Abstract
Purpose: The optimal treatment strategy for advanced or metastatic gastric, gastro-esophageal junction or esophageal carcinomas expressing Claudin-18 isoform 2 (CLDN18.2) remains inadequately defined and requires further investigation.
Methods: A systematic search was conducted to identify randomized controlled trials and single-arm studies.
Results: Four randomized controlled trials comprising five cohorts compared anti-CLDN18.2-based therapies with chemotherapy or physician's choice. Anti-CLDN18.2 therapy, primarily consisting of first-line zolbetuximab combined with chemotherapy, significantly improved progression-free survival (PFS) (hazard ratios [HR] 0.564; 95% confidence interval [CI]: 0.417-0.711) and overall survival (OS) (HR 0.716; 95% CI: 0.631-0.802), along with enhanced 1- and 2-year survival rates. However, higher rates of nausea, neutropenia, and vomiting were observed in patients treated with zolbetuximab-based regimens. A single-arm meta-analysis, which included ten cohorts from seven trials, demonstrated that antibody-drug conjugates (ADCs) exhibited greater antitumor activity compared to zolbetuximab-based regimens.
Conclusion: Anti-CLDN18.2 therapies, particularly first-line zolbetuximab plus chemotherapy, significantly improve PFS and OS in advanced gastric, gastro-esophageal junction, or esophageal carcinoma compared to standard treatments. ADCs have shown promising antitumor activity in single-arm studies, suggesting the need for confirmatory randomized trials. Standardized definitions for CLDN18.2 positivity and high expression are urgently needed.
Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD420251123719.
期刊介绍：
Future Oncology (ISSN 1479-6694) provides a forum for a new era of cancer care. The journal focuses on the most important advances and highlights their relevance in the clinical setting. Furthermore, Future Oncology delivers essential information in concise, at-a-glance article formats - vital in delivering information to an increasingly time-constrained community.
The journal takes a forward-looking stance toward the scientific and clinical issues, together with the economic and policy issues that confront us in this new era of cancer care. The journal includes literature awareness such as the latest developments in radiotherapy and immunotherapy, concise commentary and analysis, and full review articles all of which provide key findings, translational to the clinical setting.
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