{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:53:24Z","timestamp":1791942804881,"version":"4.3.4"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The treatment landscape for advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma has rapidly evolved over the last decade. The introduction of human epidermal growth factor receptor-2 (HER2)-targeted therapies and immune checkpoint inhibitors in combination with chemotherapy has led to significant improvements in overall survival in biomarker-selected patient populations. The recent Food and Drug Administration approval of zolbetuximab for patients with HER2-negative and Claudin-18 isoform 2 (CLDN18.2)-positive advanced or inoperable GEJ\/gastric adenocarcinoma has introduced further complexity into frontline therapy decisions in the absence of direct head-to-head comparisons. Here, we review data from GLOW and SPOTLIGHT trials and discuss key tumor and patient characteristics and propose a therapeutic algorithm to help guide frontline treatment decisions for patients with advanced GEJ and gastric adenocarcinoma in light of the availability of zolbetuximab.<\/jats:p>","DOI":"10.1093\/oncolo\/oyaf185","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T07:40:40Z","timestamp":1750750840000},"source":"Crossref","is-referenced-by-count":8,"title":["New tool in the toolbox: patient selection for zolbetuximab in advanced treatment-na\u00efve gastric\/gastroesophageal junction adenocarcinoma"],"prefix":"10.1093","volume":"30","author":[{"given":"Udhayvir S","family":"Grewal","sequence":"first","affiliation":[{"name":"Division of Hematology, Oncology and Blood and Marrow Transplantation, University of Iowa Hospitals and Clinics , Iowa City, IA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, UT Southwestern Medical Center , Dallas, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"2025071005111777800_CIT0001","doi-asserted-by":"publisher","first-page":"393","DOI":"10.6004\/jnccn.2023.0019","article-title":"Esophageal and esophagogastric junction cancers, Version 2.2023, NCCN clinical practice guidelines in oncology","volume":"21","author":"Ajani","year":"2023","journal-title":"J Natl Compr Canc Netw"},{"key":"2025071005111777800_CIT0002","doi-asserted-by":"publisher","first-page":"167","DOI":"10.6004\/jnccn.2022.0008","article-title":"Gastric cancer, Version 2.2022, NCCN clinical practice guidelines in oncology","volume":"20","author":"Ajani","year":"2022","journal-title":"J Natl Compr Canc Netw"},{"key":"2025071005111777800_CIT0003","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1200\/JCO.23.00441","article-title":"Immunotherapy and targeted therapy for advanced gastroesophageal cancer: ASCO guideline [published correction appears in","volume":"41","author":"Shah","year":"2023","journal-title":"J Clin Oncol"},{"key":"2025071005111777800_CIT0004","author":"U.S. Food and Drug Administration","year":"2022"},{"key":"2025071005111777800_CIT0005","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/s41571-024-00874-2","article-title":"Claudin 18.2 as a novel therapeutic target","volume":"21","author":"Nakayama","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"2025071005111777800_CIT0006","doi-asserted-by":"publisher","first-page":"7624","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":"2025071005111777800_CIT0007","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1038\/s41591-023-02465-7","article-title":"Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial","volume":"29","author":"Shah","year":"2023","journal-title":"Nat Med"},{"key":"2025071005111777800_CIT0008","doi-asserted-by":"publisher","first-page":"1655","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 [published correction appears in Lancet. 2023 Jul 22;402(10398):290. doi: 10.1016\/S0140-6736(23)01481-2] [published correction appears in Lancet. 2024 Jan 6;403(10421):30. doi: 10.1016\/S0140-6736(23)02762-9]","volume":"401","author":"Shitara","year":"2023","journal-title":"Lancet"},{"key":"2025071005111777800_CIT0009","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1200\/JCO.23.01601","article-title":"First-Line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-Year Follow-Up of the phase III checkmate 649 trial","volume":"42","author":"Janjigian","year":"2024","journal-title":"J Clin Oncol"},{"key":"2025071005111777800_CIT0010","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/s41586-022-04508-4","article-title":"Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer","volume":"603","author":"Shitara","year":"2022","journal-title":"Nature"},{"key":"2025071005111777800_CIT0011","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1001\/jamaoncol.2021.0275","article-title":"Assessment of pembrolizumab therapy for the treatment of microsatellite Instability-High gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials","volume":"7","author":"Chao","year":"2021","journal-title":"JAMA Oncol"},{"key":"2025071005111777800_CIT0012","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1056\/NEJMc2408121","article-title":"Pembrolizumab in HER2-Positive gastric cancer","volume":"391","author":"Janjigian","year":"2024","journal-title":"N Engl J Med"},{"key":"2025071005111777800_CIT0013","doi-asserted-by":"publisher","first-page":"3817","DOI":"10.1200\/JCO.23.02626","article-title":"Trastuzumab deruxtecan in advanced solid tumors with human epidermal growth factor receptor 2 amplification identified by plasma Cell-Free DNA testing: a multicenter, Single-Arm, phase II basket trial","volume":"42","author":"Yagisawa","year":"2024","journal-title":"J Clin Oncol"},{"key":"2025071005111777800_CIT0014","doi-asserted-by":"publisher","first-page":"e21339","DOI":"10.1016\/j.heliyon.2023.e21339","article-title":"Liquid biopsy based HER2 amplification status in gastric cancer patients indicates clinical response","volume":"9","author":"Klein-Scory","year":"2023","journal-title":"Heliyon"},{"key":"2025071005111777800_CIT0015","doi-asserted-by":"publisher","first-page":"e078876","DOI":"10.1136\/bmj-2023-078876","article-title":"Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial","volume":"385","author":"Qiu","year":"2024","journal-title":"BMJ"},{"key":"2025071005111777800_CIT0016","first-page":"e626","article-title":"Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial [published correction appears in","volume":"25","author":"Rha","year":"2024","journal-title":"Lancet Oncol"},{"key":"2025071005111777800_CIT0017","doi-asserted-by":"publisher","first-page":"155145","DOI":"10.1016\/j.prp.2024.155145","article-title":"Claudin-18.2 testing and its impact in the therapeutic management of patients with gastric and gastroesophageal adenocarcinomas: a literature review with expert opinion","volume":"254","author":"Angerilli","year":"2024","journal-title":"Pathol Res Pract"},{"key":"2025071005111777800_CIT0018","doi-asserted-by":"publisher","first-page":"S202","DOI":"10.1016\/j.annonc.2024.05.421","article-title":"506P Consensus guidance for management of nausea\/vomiting in patients treated with zolbetuximab + chemotherapy: a RAND\/UCLA modified Delphi panel study","volume":"35","author":"Klempner","year":"2024","journal-title":"Ann Oncol"},{"key":"2025071005111777800_CIT0019","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2503701","article-title":"Perioperative durvalumab in gastric and gastroesophageal junction cancer","author":"Janjigian","year":"2025","journal-title":"N Engl J Med."}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyaf185\/63590410\/oyaf185.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/7\/oyaf185\/63590410\/oyaf185.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/7\/oyaf185\/63590410\/oyaf185.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:11:22Z","timestamp":1752138682000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyaf185\/8174925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7,4]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyaf185","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,7]]},"article-number":"oyaf185"}}