{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:25:24Z","timestamp":1787239524475,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Zolbetuximab is a \u201cfirst-in-class\u201d chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G\/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G\/GEJ adenocarcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G\/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68\u20130.84) and PFS (HR = 0.64; 95% CI: 0.50\u20130.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82\u20131.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55\u20130.87;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002) and PFS (HR = 0.61; 95% CI: 0.44\u20130.84;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G\/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero<\/jats:ext-link>\n                      , identifier (CRD42023437126).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2023.1258347","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T07:49:10Z","timestamp":1696837750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhanpeng","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqin","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luzhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huatang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cantu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.8429","article-title":"Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group","volume":"24","author":"Van Cutsem","year":"2006","journal-title":"J Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.9378","article-title":"Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie","volume":"26","author":"Al-Batran","year":"2008","journal-title":"J Clin Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn717","article-title":"Capecitabine\/cisplatin versus 5-fluorouracil\/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial","volume":"20","author":"Kang","year":"2009","journal-title":"Ann Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1200\/JCO.21.01862","article-title":"Low programmed death-ligand 1-expressing subgroup outcomes of first-line immune checkpoint inhibitors in gastric or esophageal adenocarcinoma","volume":"40","author":"Zhao","year":"2022","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.646355","article-title":"Appropriate PD-L1 cutoff value for gastric cancer immunotherapy: A systematic review and meta-analysis","volume":"11","author":"Xie","year":"2021","journal-title":"Front Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-011-9267-1","article-title":"Claudins and cancer stem cells","volume":"7","author":"Turksen","year":"2011","journal-title":"Stem Cell Rev Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.22.010305.104219","article-title":"Tight junctions and cell polarity","volume":"22","author":"Shin","year":"2006","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.280.5.G910","article-title":"HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line","volume":"280","author":"Hollande","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyz068","article-title":"Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma","volume":"49","author":"Rohde","year":"2019","journal-title":"Jpn J Clin Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01800-8","article-title":"Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results","volume":"28","author":"Qi","year":"2022","journal-title":"Nat Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1547","article-title":"Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development","volume":"14","author":"Sahin","year":"2008","journal-title":"Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.3390\/jpm11111095","article-title":"Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas","volume":"11","author":"Pellino","year":"2021","journal-title":"J Pers Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"72","DOI":"10.21147\/j.issn.1000-9604.2022.01.07","article-title":"Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGF\u03b22\/NF-\u03baB\/Kindlin-2 axis","volume":"32","author":"Wang","year":"2022","journal-title":"Chin J Cancer Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ejca.2018.05.007","article-title":"A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer","volume":"100","author":"Sahin","year":"2018","journal-title":"Eur J Cancer."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1523096.-","article-title":"Characterization of zolbetuximab in pancreatic cancer models","volume":"8","author":"T\u00fcreci","year":"2019","journal-title":"Oncoimmunology"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.02.005","article-title":"FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma","volume":"32","author":"Sahin","year":"2021","journal-title":"Ann Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00620-7","article-title":"Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial","volume":"401","author":"Shitara","year":"2023","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.36_suppl.405736","article-title":"Zolbetuximab + CAPOX in 1L claudin-18.2+ (CLDN18.2+)\/HER2\u2013 locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG\/GEJ) adenocarcinoma: Primary phase 3 results from GLOW","volume":"41","author":"Shitara","year":"2023","journal-title":"J Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"Bmj"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"Bmj"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"Bmj"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"Bmj"},{"key":"B26","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.gene.2011.04.007","article-title":"Claudin-18 gene structure, regulation, and expression is evolutionary conserved in mammals","volume":"481","author":"T\u00fcreci","year":"2011","journal-title":"Gene"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00158.2007","article-title":"Claudin-18: a dominant tight junction protein in Barrett\u2019s esophagus and likely contributor to its acid resistance","volume":"293","author":"Jovov","year":"2007","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-186","article-title":"The claudin gene family: expression in normal and neoplastic tissues","volume":"6","author":"Hewitt","year":"2006","journal-title":"BMC Cancer."},{"key":"B29","doi-asserted-by":"publisher","first-page":"v126","DOI":"10.1093\/annonc\/mdx367.012","article-title":"Preclinical characterization of IMAB362 for the treatment of gastric carcinoma","volume":"28","author":"Mitnacht-Kraus","year":"2017","journal-title":"Ann Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15684","article-title":"Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma","volume":"114","author":"Shitara","year":"2023","journal-title":"Cancer Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz199","article-title":"A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study","volume":"30","author":"T\u00fcreci","year":"2019","journal-title":"Ann Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-0204","article-title":"ILUSTRO: phase 2 multicohort trial of zolbetuximab in patients with advanced or metastatic claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma","author":"Klempner","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0508-4","article-title":"Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases","volume":"121","author":"Coati","year":"2019","journal-title":"Br J Cancer."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.5230\/jgc.2020.20.e33","article-title":"Clinical significance of CLDN18.2 expression in metastatic diffuse-type gastric cancer","volume":"20","author":"Kim","year":"2020","journal-title":"J Gastric Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2020-5183","article-title":"Abstract 5183: The preclinical characterization of TST001, a novel humanized anti-claudin18.2 mAb with enhanced binding affinity and anti-tumor activity","volume":"80","author":"Teng","year":"2020","journal-title":"Cancer Res"},{"key":"B36","unstructured":"TRANSCENTA, Osemitamab plus Capecitabine and Oxaliplatin (CAPOX) as the First-LineTreatment of Advanced G\/GEJ Cancer -Updated Efficacy Data per Claudin 18.2 Expression Level from Study TranStar102\/TST001-1002-Cohort C"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1258347\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T07:49:14Z","timestamp":1696837754000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1258347\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,9]]},"references-count":36,"alternative-id":["10.3389\/fonc.2023.1258347"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1258347","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,9]]},"article-number":"1258347"}}