{"entity":{"id":"her2-gastric-sequence","kind":"pairing","name":"HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd","aka":[],"tldr":"For HER2-positive stomach cancer, an antibody-plus-chemotherapy first, then Enhertu when it progresses. Both steps now have phase 3 proof.","summary":"First line: trastuzumab + chemotherapy + pembrolizumab (KEYNOTE-811, PD-L1 CPS ≥1) or zanidatamab + chemotherapy ± tislelizumab (HERIZON-GEA-01, PFS 12.4 vs 8.1 months). Second line: T-DXd (DESTINY-Gastric04, OS 14.7 vs 11.4 months). HER2 loss after first-line therapy occurs in ~30%, so re-biopsy or ctDNA before T-DXd is advisable.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05152147: HERIZON-GEA-01","url":"https://clinicaltrials.gov/study/NCT05152147"},{"label":"ClinicalTrials.gov NCT04704934: DESTINY-Gastric04","url":"https://clinicaltrials.gov/study/NCT04704934"}],"tags":[],"related":[],"cancers":["gastric"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["zanidatamab","trastuzumab","trastuzumab-deruxtecan","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["herizon-gea-01","destiny-gastric04","toga"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"zanidatamab","b":"trastuzumab-deruxtecan","rationale":"Antibody blockade and ADC payload delivery are distinct mechanisms; HER2 expression usually persists at progression.","evidence":"Phase 3 for each step; the sequence itself is inferred, not randomised.","pairingType":"sequence"},"route":"/pairings/her2-gastric-sequence/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"gastric-her2-positive","kind":"cancer","name":"HER2-positive gastric cancer","route":"/cancers/gastric-her2-positive/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"zanidatamab","kind":"drug","name":"Zanidatamab","route":"/drugs/zanidatamab/"}],"trial":[{"id":"destiny-gastric04","kind":"trial","name":"DESTINY-Gastric04","route":"/trials/destiny-gastric04/"},{"id":"herizon-gea-01","kind":"trial","name":"HERIZON-GEA-01","route":"/trials/herizon-gea-01/"},{"id":"toga","kind":"trial","name":"ToGA","route":"/trials/toga/"}]}}