{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:55:36Z","timestamp":1791190536655,"version":"4.1.0"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"abstract":"<jats:p>Purpose In HER2-negative metastatic gastric cancer, immune checkpoint inhibitors (ICIs) and CLDN18.2-targeted antibody zolbetuximab, combined with chemotherapy (CT), have emerged as first line options. Treatment selection is relatively straightforward in microsatellite instability\u2013high (MSI-H), PD-L1 combined positive score (CPS)\u2013high\/negative disease, but uncertainty persists in overlapping biomarkers\u2014particularly CLDN18.2-positive tumors with low-to-intermediate PD-L1 CPS\u2014where direct comparative evidence is lacking. Methods Individual patient data were reconstructed from published Kaplan\u2013Meier curves of pivotal phase III trials (SPOTLIGHT\/GLOW, CheckMate-649, KEYNOTE-859). Descriptive, unadjusted indirect comparisons of progression-free survival (PFS) and overall survival (OS) were performed using pooled CT as common reference. Findings were interpreted within a biomarker-oriented framework incorporating PD-L1 CPS, CLDN18.2 expression, MSI status and treatment mechanisms. Results PFS benefit versus pooled CT was marked with zolbetuximab plus CT (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.53\u20130.68), but more modest with pooled ICI-based regimens (HR 0.81, 95% CI 0.75\u20130.88). Both strategies improved OS. CLDN18.2-positive tumors are predominantly PD-L1 CPS\u2013low, a biological context where ICI benefit may be heterogeneous. Conversely, zolbetuximab demonstrated consistent efficacy in this selected population; leveraging its established mechanism of direct CLDN18.2-targeting and innate immune activation, it provides a biomarker-directed therapeutic option that addresses the clinical gap in PD-L1 CPS\u2013low disease. Conclusions Population-level efficacy estimates should not be interpreted as therapeutic interchangeability between ICIs and CLDN18.2-targeted therapy. Without direct comparative data, treatment selection in CLDN18.2-positive, PD-L1 CPS\u2013low disease requires integration of biomarker biology and clinical context. This biomarker-informed framework supports clinical decision-making under uncertainty.<\/jats:p>","DOI":"10.1159\/ocl\/aebag012","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:53:38Z","timestamp":1788616418000},"source":"Crossref","is-referenced-by-count":0,"title":["Biomarker-Oriented Contextual Analysis of First-Line Zolbetuximab and Immunotherapy-Based Strategies in HER2-Negative Metastatic Gastric Cancer"],"prefix":"10.1159","author":[{"given":"Arianna","family":"Sabatini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Bengala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Picone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,9,9]]},"container-title":["Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/ocl\/aebag012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:31:21Z","timestamp":1791189081000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/ocl\/aebag012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/ocl\/aebag012","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.33446320","asserted-by":"subject"}]},"ISSN":["0030-2414","1423-0232"],"issn-type":[{"value":"0030-2414","type":"print"},{"value":"1423-0232","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}