{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:47:30Z","timestamp":1792075650647,"version":"4.4.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastrointest Canc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Zanidatamab is a novel HER2-targeted antibody that binds to two non-overlapping extracellular domains of the HER2 receptor. Early-phase trials have shown clinical benefit of first-line Zanidatamab in patients with advanced HER2-positive esophageal adenocarcinoma (GEA). We performed a meta-analysis to evaluate the efficacy and safety of zanidatamab in this patient population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase, Cochrane, ASCO, and ESMO databases for studies examining zanidatamab as first-line treatment in patients with HER2-positive advanced GEA. Outcomes of interest included progression-free survival (PFS); objective response rate (ORR); disease control rate (DCR); duration of response (DOR); and incidence of adverse events (AEs). Analyses were presented as median or proportions in percentages with 95% confidence intervals (CIs). Random-effect models were used for analysis, which were carried out using R software (v4.5.2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three clinical trials involving 685 patients with advanced HER2-positive GEA treated with zanidatamab in combination with chemotherapy and\/or tislelizumab were included. Overall, the reconstructed pooled median OS was 26.05 months (95% CI: 23.60-30.04), while the pooled median PFS was 12.61 months (95% CI: 11.05\u201314.60). The pooled ORR was 70% (95% CI, 67\u201374), DCR was 96% (95% CI, 78\u2013100), and median DOR was 17.11 months (95% CI, 13.07\u201322.40). Treatment-related diarrhea leading to dose reduction was observed in 16% (95% CI, 1%-75%) of patients. Treatment discontinuation due to any cause rate was 20% (95% CI, 3%-44%). Serious treatment-emergent AEs occurred in 66% (95% CI, 50%-81%) of patients. Common any-grade AEs included diarrhea (89%; 95% CI, 75%-98%), nausea (60%; 95% CI, 45%-74%), and infusion-related reactions (30%; 95% CI, 19%-43%). Grade\u2009\u2265\u20093 diarrhea, nausea, and treatment-related AEs rates were as follows: 26% (95% CI, 19%-34%), 5% (95% CI, 2%-13%), and 65% (95% CI, 58%-71%), respectively. Other important AEs include immune-mediated AEs (25% incidence rate), left ventricular dysfunction (6% incidence rate), and non-infectious pulmonary toxicity (4% incidence rate).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our pooled analyses suggest that zanidatamab exhibits meaningful activity as first-line treatment of advanced HER2-positive GEA. Yet, concerning toxicity rates were also consistently reported across studies. Future randomized studies are needed to further explore its activity and safety profile in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12029-026-01608-6","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:30:34Z","timestamp":1792074634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Meta-Analysis on Outcomes of Zanidatamab Plus Chemotherapy in Patients with Advanced HER2-positive Gastroesophageal Adenocarcinoma"],"prefix":"10.1007","volume":"57","author":[{"given":"Henrique Jin Son","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murilo Lauria Freire","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Gil-Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Rossato de Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Borsarelli Carvalho","family":"Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago Cordeiro","family":"Felismino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"issue":"20","key":"1608_CR1","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1056\/NEJMoa2517729","volume":"394","author":"K Shitara","year":"2026","unstructured":"Shitara K, Elimova E, Liu T, Tabernero J, Lee KW, Schenker M, et al. Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer. N Engl J Med. 2026;394(20):2002\u201314. https:\/\/doi.org\/10.1056\/NEJMoa2517729.","journal-title":"N Engl J Med"},{"issue":"3","key":"1608_CR2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u201363. https:\/\/doi.org\/10.3322\/caac.21834.","journal-title":"CA Cancer J Clin"},{"issue":"3","key":"1608_CR3","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1007\/s10120-014-0402-y","volume":"18","author":"E Van Cutsem","year":"2015","unstructured":"Van Cutsem E, Bang YJ, Feng-yi F, Xu JM, Lee KW, Jiao SC, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476\u201384. https:\/\/doi.org\/10.1007\/s10120-014-0402-y.","journal-title":"Gastric Cancer"},{"issue":"8","key":"1608_CR4","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41571-021-00492-2","volume":"18","author":"Y Nakamura","year":"2021","unstructured":"Nakamura Y, Kawazoe A, Lordick F, Janjigian YY, Shitara K. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm. Nat Rev Clin Oncol. 2021;18(8):473\u201387. https:\/\/doi.org\/10.1038\/s41571-021-00492-2.","journal-title":"Nat Rev Clin Oncol"},{"issue":"10","key":"1608_CR5","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1016\/S1470-2045(18)30481-9","volume":"19","author":"J Tabernero","year":"2018","unstructured":"Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018;19(10):1372\u201384. https:\/\/doi.org\/10.1016\/S1470-2045(18)30481-9.","journal-title":"Lancet Oncol"},{"issue":"10418","key":"1608_CR6","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1016\/S0140-6736(23)02033-0","volume":"402","author":"YY Janjigian","year":"2023","unstructured":"Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023;402(10418):2197\u2013208. https:\/\/doi.org\/10.1016\/S0140-6736(23)02033-0.","journal-title":"Lancet"},{"issue":"1","key":"1608_CR7","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1038\/s41467-023-37029-3","volume":"14","author":"NE Weisser","year":"2023","unstructured":"Weisser NE, Sanches M, Escobar-Cabrera E, O\u2019Toole J, Whalen E, Chan PWY, et al. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity. Nat Commun. 2023;14(1):1394. https:\/\/doi.org\/10.1038\/s41467-023-37029-3.","journal-title":"Nat Commun"},{"key":"1608_CR8","unstructured":"Higgins JPTTJ. Cochrane Handbook for Systematic Reviews of Interventions [Internet]. Version 6.5, 2024 (updated August 2024). The Cochrane Collaboration. Available from: https:\/\/training.cochrane.org\/handbook\/current"},{"key":"1608_CR9","doi-asserted-by":"publisher","unstructured":"Sterne JAC, Savovi\u0107 J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;l4898. https:\/\/doi.org\/10.1136\/bmj.l4898.","DOI":"10.1136\/bmj.l4898"},{"issue":"4","key":"1608_CR10","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1056\/NEJMoa2503119","volume":"393","author":"K Shitara","year":"2025","unstructured":"Shitara K, Van Cutsem E, G\u00fcm\u00fc\u015f M, Lonardi S, De La Fouchardi\u00e8re C, Coutzac C, et al. Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer. N Engl J Med. 2025;393(4):336\u201348. https:\/\/doi.org\/10.1056\/NEJMoa2503119.","journal-title":"N Engl J Med"},{"issue":"4suppl","key":"1608_CR11","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1200\/JCO.2025.43.4_suppl.448","volume":"43","author":"YY Janjigian","year":"2025","unstructured":"Janjigian YY, Van Laarhoven HWM, Rha SY, Kozlov V, Oh DY, Gravina A, et al. Updated results from the trastuzumab deruxtecan (T-DXd) 5.4\u00a0mg\/kg triplet combination of DESTINY-Gastric03 (DG-03): First-line (1L) T-DXd with fluoropyrimidine (FP) and pembrolizumab in advanced\/metastatic HER2-positive (HER2+) esophageal adenocarcinoma, gastric cancer (GC), or gastroesophageal junction adenocarcinoma (GEJA). JCO. 2025;43(4suppl):448\u2013448. https:\/\/doi.org\/10.1200\/JCO.2025.43.4_suppl.448.","journal-title":"JCO"},{"key":"1608_CR12","doi-asserted-by":"publisher","first-page":"102418","DOI":"10.1016\/j.ctrv.2022.102418","volume":"108","author":"D Blang\u00e9","year":"2022","unstructured":"Blang\u00e9 D, Stroes CI, Derks S, Bijlsma MF, Van Laarhoven HWM. Resistance mechanisms to HER2-targeted therapy in gastroesophageal adenocarcinoma: A systematic review. Cancer Treat Rev. 2022;108:102418. https:\/\/doi.org\/10.1016\/j.ctrv.2022.102418.","journal-title":"Cancer Treat Rev"},{"key":"1608_CR13","doi-asserted-by":"publisher","unstructured":"Peng Z, Li C, Wang X, Zhang Y, Yang L, Huang X, et al. Disitamab vedotin (DV) plus toripalimab (Tor) and chemotherapy (Chemo)\/trastuzumab (Tra) for first-line (1L) HER2-expressing locally advanced or metastatic (la\/m) gastric cancer (GC): Updated results from the RC48-C027 trial. J Clin Oncol. 2026;44(17suppl). https:\/\/doi.org\/10.1200\/JCO.2026.44.17_suppl.LBA4026.","DOI":"10.1200\/JCO.2026.44.17_suppl.LBA4026"},{"issue":"4","key":"1608_CR14","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1200\/JCO.22.00575","volume":"41","author":"K Yamaguchi","year":"2023","unstructured":"Yamaguchi K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab Deruxtecan in Anti\u2013Human Epidermal Growth Factor Receptor 2 Treatment\u2013Naive Patients With Human Epidermal Growth Factor Receptor 2\u2013Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. JCO. 2023;41(4):816\u201325. https:\/\/doi.org\/10.1200\/JCO.22.00575.","journal-title":"JCO"}],"container-title":["Journal of Gastrointestinal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01608-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12029-026-01608-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01608-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:30:36Z","timestamp":1792074636000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12029-026-01608-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1608"],"URL":"https:\/\/doi.org\/10.1007\/s12029-026-01608-6","relation":{},"ISSN":["1941-6636"],"issn-type":[{"value":"1941-6636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"20 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"238"}}