{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:05:35Z","timestamp":1784761535997,"version":"3.55.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>First-line treatment of HER2-positive advanced gastric\/GEJ adenocarcinoma now includes pembrolizumab added to trastuzumab plus chemotherapy (KEYNOTE-811). Zanidatamab, a bispecific anti-HER2 antibody, improved outcomes in HERIZON-GEA-01 but has not been directly compared with this standard.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Scopus, and the ASCO\/ESMO libraries for phase II\/III trials of previously untreated HER2-positive metastatic gastric\/GEJ adenocarcinoma. Individual patient data were reconstructed from published Kaplan-Meier curves. Cox frailty models estimated hazard ratios using the pembrolizumab regimen as the reference. Restricted mean survival time analysis was performed at 12, 24, and 36\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine trials were included: trastuzumab\u2009+\u2009chemotherapy (n\u2009=\u20091466), pembrolizumab\u2009+\u2009trastuzumab\u2009+\u2009chemotherapy (n\u2009=\u2009430), zanidatamab\u2009+\u2009chemotherapy (n\u2009=\u2009350), and zanidatamab\u2009+\u2009tislelizumab\u2009+\u2009chemotherapy (n\u2009=\u2009335). Median PFS was 12.5\u2009months with both zanidatamab regimens vs 10.0\u2009months with pembrolizumab. The zanidatamab-tislelizumab triplet significantly reduced progression hazard (HR, 0.78, 95% CI, 0.62-0.99; P\u2009=\u20090.042). Median OS was 27.0 and 25.3\u2009months with zanidatamab arms vs 20.3\u2009months with pembrolizumab. Both zanidatamab arms showed significantly longer OS at 36\u2009months by RMST.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Zanidatamab-based regimens were associated with longer PFS and OS than the pembrolizumab standard, though direct randomized comparisons are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag270","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:35:57Z","timestamp":1784028957000},"source":"Crossref","is-referenced-by-count":0,"title":["Zanidatamab vs trastuzumab with or without PD-1 blockade in HER2-positive metastatic gastric cancer: a reconstructed patient-level pooled analysis"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-4207","authenticated-orcid":false,"given":"Federico","family":"Nichetti","sequence":"first","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]},{"name":"University of Padua Department of Surgery, Oncology and Gastroenterology, , Padua, 35122,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1319-6052","authenticated-orcid":false,"given":"Floriana","family":"Nappo","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bof","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]},{"name":"University of Padua Department of Surgery, Oncology and Gastroenterology, , Padua, 35122,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Bosa","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]},{"name":"University of Padua Department of Surgery, Oncology and Gastroenterology, , Padua, 35122,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mattiuzzo","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Maddalena","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Caterina","family":"De Grandis","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Murgioni","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bergamo","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lonardi","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padua, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026072218470378800_oyag270-B1","doi-asserted-by":"crossref","first-page":"687","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":"2026072218470378800_oyag270-B2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41571-026-01134-1","article-title":"Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics","volume":"23","author":"Choo","year":"2026","journal-title":"Nat Rev Clin Oncol"},{"key":"2026072218470378800_oyag270-B3","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.2217\/pgs-2018-0077","article-title":"Genomic markers of resistance to targeted treatments in gastric cancer: potential new treatment strategies","volume":"19","author":"Raimondi","year":"2018","journal-title":"Pharmacogenomics"},{"key":"2026072218470378800_oyag270-B4","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41586-021-04161-3","article-title":"The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer","volume":"600","author":"Janjigian","year":"2021","journal-title":"Nature"},{"key":"2026072218470378800_oyag270-B5","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/S0140-6736(23)02033-0","article-title":"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","volume":"402","author":"Janjigian","year":"2023","journal-title":"Lancet"},{"key":"2026072218470378800_oyag270-B6","first-page":"1923","article-title":"FDA approval summary: pembrolizumab for the treatment of HER2-Positive gastric cancer","volume":"2026","author":"Casak","journal-title":"Clin Cancer Res."},{"key":"2026072218470378800_oyag270-B7","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1056\/NEJMoa2517729","article-title":"Zanidatamab with and without tislelizumab in HER2-positive gastroesophageal cancer","volume":"394","author":"Shitara","year":"2026","journal-title":"N Engl J Med"},{"key":"2026072218470378800_oyag270-B8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1471-2288-12-9","article-title":"Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves","volume":"12","author":"Guyot","year":"2012","journal-title":"BMC Med Res Methodol"},{"key":"2026072218470378800_oyag270-B9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12874-022-01567-z","article-title":"KMSubtraction: reconstruction of unreported subgroup survival data utilizing published Kaplan-Meier survival curves","volume":"22","author":"Zhao","year":"2022","journal-title":"BMC Med Res Methodol"},{"key":"2026072218470378800_oyag270-B10","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S1470-2045(25)00287-6","article-title":"Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: primary results of a multicentre, single-arm, phase 2 study","volume":"26","author":"Elimova","year":"2025","journal-title":"Lancet Oncol"},{"key":"2026072218470378800_oyag270-B11","first-page":"LBA285","article-title":"Zanidatamab\u2009+\u2009chemotherapy (CT) \u00b1 tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): primary analysis from HERIZON-GEA-01","volume":"44","author":"Elimova","year":"2026","journal-title":"J Clin Oncol"},{"key":"2026072218470378800_oyag270-B12","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S1470-2045(20)30169-8","article-title":"First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial","volume":"21","author":"Janjigian","year":"2020","journal-title":"Lancet Oncol"},{"key":"2026072218470378800_oyag270-B13","doi-asserted-by":"crossref","first-page":"6002","DOI":"10.1038\/s41467-022-33267-z","article-title":"A single arm phase Ib\/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer","volume":"13","author":"Lee","year":"2022","journal-title":"Nat Commun"},{"key":"2026072218470378800_oyag270-B14","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1158\/1078-0432.CCR-24-4295","article-title":"Phase Ib\/II study of zanidatamab in combination with tislelizumab and chemotherapy in first-line HER2-positive gastric\/gastroesophageal junction adenocarcinoma","volume":"32","author":"Lee","year":"2026","journal-title":"Clin Cancer Res"},{"key":"2026072218470378800_oyag270-B15","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1200\/JCO.2016.71.6852","article-title":"HELOISE: phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma","volume":"35","author":"Shah","year":"2017","journal-title":"J Clin Oncol"},{"key":"2026072218470378800_oyag270-B16","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/S1470-2045(18)30481-9","article-title":"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","volume":"19","author":"Tabernero","year":"2018","journal-title":"Lancet Oncol"},{"key":"2026072218470378800_oyag270-B17","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1056\/NEJMoa2503119","article-title":"Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer","volume":"393","author":"Shitara","year":"2025","journal-title":"N Engl J Med"},{"key":"2026072218470378800_oyag270-B18","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s10120-026-01736-9","article-title":"Clinical impact of intratumoral HER2 heterogeneity on trastuzumab deruxtecan efficacy in patients with HER2-positive gastric cancer","volume":"29","author":"Yoshino","year":"2026","journal-title":"Gastric Cancer"},{"key":"2026072218470378800_oyag270-B19","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/s41467-023-37029-3","article-title":"An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity","volume":"14","author":"Weisser","year":"2023","journal-title":"Nat Commun"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag270\/68770646\/oyag270.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/8\/oyag270\/68770646\/oyag270.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/8\/oyag270\/68770646\/oyag270.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:47:09Z","timestamp":1784760429000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyag270\/8733881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":19,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,7,8]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyag270","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,7,8]]},"article-number":"oyag270"}}