Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"November 04, 2026 5 min read Add topic to email alerts Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on . ” data-action=subscribe> Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com. Back to Healio Key takeaways: Zanidatamab regimens significantly improved survival compared with trastuzumab plus chemotherapy for patients with gastroesophageal adenocarcinoma. Diarrhea is a common adverse event. First-line zanidatamab-hrii plus chemotherapy, without or with tislelizumab-jsgr, extended survival 24% and 35% vs. trastuzumab plus chemotherapy for those with locally advanced or metastatic gastroesophageal adenocarcinoma. Findings from the randomized phase 3 HERIZON-GEA-01 trial, presented at European Society for Medical Oncology Congress, showed that zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals) combinations extended median OS by 3 and 8 months. Data derived from Shitara K, et al. Abstract LBA79. Presented at: European Society for Medical Oncology Congress; Oct. 23-27, 2026; Madrid. Geoffrey Y. Ku \u201cThese results are truly ground-breaking and highlight how much the first-line treatment landscape for HER2-positive advanced gastroesophageal adenocarcinoma has evolved,\u201d Geoffrey Y. Ku, MD, gastrointestinal oncologist at Memorial Sloan Kettering Cancer Center and co-author of the HERIZON-GEA-01 study, told Healio. \u201cWe are now seeing survival outcomes that would have been difficult to envision when trastuzumab first became the standard HER2-directed therapy in this setting 16 years ago.\u201d Long-term survival \u2018uncommon\u2019 The Trastuzumab for Gastric Cancer trial established trastuzumab (Herceptin, Genentech) plus chemotherapy as standard first-line treatment for HER2-positive advanced gastroesophageal adenocarcinoma in 2010, improving median OS to 13.8 months. Recent research has shown that adding pembrolizumab (Keytruda, Merck) could extend median OS to roughly 20 months for patients with PD-L1-postive disease. However, long-term survival remains \u201cuncommon,\u201d Ku said. \u201cHERIZON-GEA-01 was designed to determine whether zanidatamab, a bispecific HER2-directed antibody that binds to two distinct sites on HER2, could improve outcomes by providing a new HER2-targeted backbone,\u201d he explained. Researchers evaluated zanidatamab-hrii plus chemotherapy, with or without tislelizumab-jsgr (Tevimbra, BeOne Medicines USA), an anti-PD-L1 antibody, against trastuzumab plus chemotherapy. They randomly assigned 914 patients 1:1:1 to receive IV zanidatamab-hrii (< 70 kg, 1,800 mg; 70 kg, 2,400 mg) every 3 weeks plus chemotherapy with (n = 302) or without (n = 304) 200 mg IV tislelizumab-jsgr every 3 weeks, or trastuzumab plus chemotherapy (n = 308). PFS and OS served as primary endpoints. The FDA approved zanidatamab-hrii combinations for unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma in August based on results from the first interim analysis. \u2018Truly remarkable\u2019 In the second and final analysis, the zanidatamab-hrii plus chemotherapy arm had significantly improved OS compared with trastuzumab (median: 22.9 months vs. 19.6 months; HR = 0.76; 95% CI, 0.62-0.93). Researchers observed benefits across most subgroups. Notably, patients with HER2-positive IHC 3+ tumors had significant improvement (HR = 0.71; 95% CI, 0.57-0.88) but those with HER2-positive, IHC 2+\/ISH+ disease did not. \u201cHowever, there were only about 50 patients with HER2-positive, IHC 2+\/ISH+ tumors in each group,\u201d Ku said. \u201cEven small imbalances could have confounded these results.\u201d Patients who received tislelizumab-jsgr with zanidatamab-hrii also had significantly improved OS compared with the trastuzumab arm (median: 27 months vs. 19.6 months; HR = 0.65; 95% CI, 0.52-0.8). This translated into a 3-year OS rate of 39.8% vs. 22.9%. \u201cIt is truly remarkable that 40% of patients were alive at 3 years, which offers unprecedented hope for our patients,\u201d Ku said. Ku and colleagues observed benefits across most subgroups, including among patients with PD-L1-negative (HR = 0.5; 95% CI, 0.35-0.73) and positive (HR = 0.68; 95% CI, 0.52-0.89) disease. Ku described the PD-L1 findings as an \u201cextremely pleasant surprise.\u201d The tislelizumab-jsgr arm had a \u201cclinically meaningful\u201d improvement in OS compared with the zanidatamab-hrii only arm (median: 27 months vs. 22.9 months; 3-year rate: 39.8% vs. 31.5%), but this failed to meet statistical significance, Ku said. However, researchers noted the study was not powered to compare those two experimental treatments. Researchers observed similar OS rates based on PD-L1 expression, too. \u201cTo me, these results are directionally and conceptually comparable to those seen in the KEYNOTE-811 study that showed benefit for adding pembrolizumab to trastuzumab and chemotherapy, and establishes that zanidatamab plus tislelizumab and chemotherapy should be offered to patients who are candidates for immunotherapy,\u201d Ku said. Compared with the trastuzumab arm, patients achieved significantly longer PFS if they received the doublet (median: 12.4 months vs. 8.3 months; HR = 0.65; 95% CI, 0.53-0.8) or triplet (median: 12.7 months; HR = 0.61; 95% CI, 0.5-0.76). The triplet arm had the highest mean duration of treatment (64.1 weeks), followed by the doublet (52.6 weeks) and trastuzumab (42.3 weeks). All three arms had similar rates of any grade treatment-emergent and treatment-related adverse events. However, the triple had higher rates of grade 3 or worse treatment-related adverse events than the doublet and trastuzumab arms (72.4% vs. 59% and 59.9%). Similarly, patients who received tislelizumab-jsgr had the highest rate of serious treatment-related adverse events (42.2% vs. 28.5% vs. 20.5%). Any-grade diarrhea occurred in 83% of patients who received tislelizumab-jsgr and 79% who received the doublet, compared with 53.3% in the trastuzumab arm. Grade 3 or worse diarrhea followed a similar pattern (25.2% vs. 20% vs. 12.9%). \u201cZanidatamab plus tislelizumab and chemotherapy led to severe grade 3\/4 diarrhea in 25% of patients, despite mandatory loperamide prophylaxis for the first 7 days,\u201d Ku said. \u201cThankfully, the diarrhea resolved within 3 weeks with appropriate management, and only 4% of patients had to discontinue zanidatamab because of it. Therefore, a critical issue for clinicians and patients alike in order to realize the benefits of this regimen is aggressive and comprehensive management of the diarrhea. This management involves patient and physician education, close communication and early recognition of worsening diarrhea so that additional anti-diarrhea medications, supportive treatments and appropriate delays and reductions in chemotherapy can be instituted.\u201d The tislelizumab-jsgr arm had the highest rate of treatment-related adverse events leading to death (2.4%), followed by trastuzumab (1.3%) and the doublet<\/p>\n","protected":false},"author":1,"featured_media":4252,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-4251","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts\/4251","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=4251"}],"version-history":[{"count":0,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts\/4251\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/media\/4252"}],"wp:attachment":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4251"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4251"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4251"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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