Zanidatamab-hrii combinations improved survival in first-line HER2-positive advanced gastroesophageal adenocarcinoma

1. In company-reported phase 3 results, zanidatamab-hrii plus chemotherapy improved overall survival versus trastuzumab plus chemotherapy, with median overall survival of 22.9 versus 19.6 months (hazard ratio [HR], 0.76; P=0.0088).

2. Zanidatamab-hrii plus tislelizumab and chemotherapy produced median overall survival of 27.0 months and estimated 36-month overall survival of 39.8%; the safety profile was unchanged with longer follow-up.

Evidence Rating Level: 2 (Good)

2MM Brief: Jazz Pharmaceuticals reported updated overall survival results for first-line treatment of adults with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic gastroesophageal adenocarcinoma, a disease setting in which long-term survival remains difficult to achieve. The phase 3 HERIZON-GEA-01 trial evaluated zanidatamab-hrii plus chemotherapy, with or without tislelizumab, compared with trastuzumab plus chemotherapy. At the second interim and final formal analysis, median follow-up was 35.3 months. Zanidatamab-hrii plus tislelizumab and chemotherapy produced a median overall survival of 27.0 months (95% confidence interval [CI], 23.7-32.2), compared with 19.6 months with trastuzumab plus chemotherapy; the hazard ratio was 0.65 (95% CI, 0.52-0.80). Estimated 36-month overall survival was 39.8%, 31.5%, and 22.9% with zanidatamab-hrii plus tislelizumab and chemotherapy, zanidatamab-hrii plus chemotherapy, and trastuzumab plus chemotherapy, respectively. Zanidatamab-hrii plus chemotherapy also improved overall survival versus trastuzumab plus chemotherapy, with median overall survival of 22.9 months (95% CI, 19.9-27.6) versus 19.6 months (95% CI, 16.9-22.2; HR, 0.76; 95% CI, 0.62-0.93; P=0.0088). The comparison between the 2 zanidatamab-hrii regimens showed a median overall survival of 27.0 versus 22.9 months (HR, 0.81; 95% CI, 0.65-1.00; P=0.0502), a difference that did not reach statistical significance. Mean duration of treatment was 64.1 weeks, 52.6 weeks, and 42.3 weeks, respectively. Jazz Pharmaceuticals said the safety profiles of both zanidatamab-hrii regimens were unchanged from the first interim analysis. These are company-reported results presented at the European Society for Medical Oncology Congress 2026 and have not been peer reviewed in their updated form; earlier HERIZON-GEA-01 results were published in The New England Journal of Medicine. This single trial supports durable survival with zanidatamab-hrii-containing regimens, but the updated findings remain subject to peer-reviewed assessment.

Source: Jazz Pharmaceuticals.

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