{"id":19724,"date":"2024-11-13T20:49:50","date_gmt":"2024-11-13T19:49:50","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/11\/13\/inflammatory-stress-determines-the-need-for-chemotherapy-in-patients-with-her2-positive-esophagogastric-adenocarcinoma-receiving-targeted-and-immunotherapy\/"},"modified":"2024-11-13T20:49:50","modified_gmt":"2024-11-13T19:49:50","slug":"inflammatory-stress-determines-the-need-for-chemotherapy-in-patients-with-her2-positive-esophagogastric-adenocarcinoma-receiving-targeted-and-immunotherapy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/11\/13\/inflammatory-stress-determines-the-need-for-chemotherapy-in-patients-with-her2-positive-esophagogastric-adenocarcinoma-receiving-targeted-and-immunotherapy\/","title":{"rendered":"Inflammatory stress determines the need for chemotherapy in patients with HER2-positive esophagogastric adenocarcinoma receiving targeted and immunotherapy"},"content":{"rendered":"<div>\n<p>Cancer Immunol Res. 2024 Nov 11. doi: 10.1158\/2326-6066.CIR-24-0561. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>Anti-PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma (EGA), but long-term survival remains limited. Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison to a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease. The 12-month overall survival (OS) showed no statistical difference between the arms, with 57% OS (95% CI: 41%-71%) in the Ipi arm and 70% OS (95% CI: 54%-82%) in the FOLFOX arm. Crossing of the survival curves indicated a potential long-term benefit for some patients within the Ipi arm, but early progressors in the Ipi arm underlined the need for biomarker-guided strategies to optimize treatment selection. To this end, metabolomic and cytokine analysis demonstrated elevated levels of normetanephrine, cortisol, and interleukin 6 (IL-6) in immunotherapy-unresponsive patients in the Ipi arm, suggesting a role for systemic inflammatory stress in modulating antitumor immune responses. Patients with this signature also showed an increased neutrophil-to-lymphocyte ratio (NLR) that persisted in the Ipi arm, but not in the FOLFOX arm, and strongly correlated with survival. Furthermore, a low NLR characterized patients benefiting from immune- and targeted therapy without the need for additional chemotherapy. This data suggests that patient selection based on inflammatory stress-driven immune changes could help to customize first-line treatment in patients with advanced HER2-positive EGA to potentially improve long-term survival.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39527097\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20241113144950&amp;v=2.18.0.post9+e462414\">39527097<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0561\">10.1158\/2326-6066.CIR-24-0561<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2024 Nov 11. doi: 10.1158\/2326-6066.CIR-24-0561. Online ahead of print. ABSTRACT Anti-PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma (EGA), but long-term survival remains limited. Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, &#8230; <a title=\"Inflammatory stress determines the need for chemotherapy in patients with HER2-positive esophagogastric adenocarcinoma receiving targeted and immunotherapy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/11\/13\/inflammatory-stress-determines-the-need-for-chemotherapy-in-patients-with-her2-positive-esophagogastric-adenocarcinoma-receiving-targeted-and-immunotherapy\/\" aria-label=\"Read more about Inflammatory stress determines the need for chemotherapy in patients with HER2-positive esophagogastric adenocarcinoma receiving targeted and immunotherapy\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-19724","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19724","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=19724"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19724\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=19724"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=19724"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=19724"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}