GI Oncology Daily Digest

On August 25, 2026 the FDA approved two zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals) regimens for previously untreated, unresectable locally advanced or metastatic HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma — and the two indications are deliberately not the same. The triplet, zanidatamab plus tislelizumab-jsgr (Tevimbra) plus fluoropyrimidine- and platinum-containing chemotherapy, is approved across HER2 IHC 3+ and IHC 2+/ISH+ disease with no PD-L1 requirement; the chemotherapy doublet, zanidatamab plus fluoropyrimidine/platinum without immunotherapy, is restricted to IHC 3+. In HERIZON-GEA-01 (NCT05152147), a three-arm 1:1:1 global trial against trastuzumab plus chemotherapy with dual primary endpoints of BICR-assessed PFS and OS, the triplet improved median OS to 26.4 months (95% CI 21.5–30.3) versus 19.2 months (16.8–21.8), HR 0.72 (0.57–0.90), p=0.0043, and median PFS to 12.4 months (9.8–18.5) versus 8.1 months (7.0–8.9), HR 0.63 (0.51–0.78), p<0.0001. The zanidatamab-plus-chemotherapy arm improved PFS but its interim OS was not statistically significant, and exploratory analysis attributed the effect primarily to IHC 3+ tumours, where median PFS was 14.2 versus 7.6 months (HR 0.55, 0.43–0.69) — which is precisely where the label draws its line. Zanidatamab carries a boxed warning for diarrhoea and embryo-fetal toxicity plus warnings for left ventricular dysfunction and infusion-related reactions, and two Roche/Ventana companion diagnostics (PATHWAY anti-HER-2/neu 4B5 and VENTANA HER2 Dual ISH) were approved the same day, so HER2 scoring now determines which of the two regimens a patient is eligible for rather than simply establishing HER2 positivity.