# HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd

Source: https://onco.cc/pairings/her2-gastric-sequence/  
OnCo record `her2-gastric-sequence` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Zanidatamab + Trastuzumab deruxtecan
- Type: sequence
- 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.

## Sources

- ClinicalTrials.gov NCT05152147: HERIZON-GEA-01: https://clinicaltrials.gov/study/NCT05152147
- ClinicalTrials.gov NCT04704934: DESTINY-Gastric04: https://clinicaltrials.gov/study/NCT04704934

## Connected records

- cancers: [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [HER2-positive gastric cancer](https://onco.cc/cancers/gastric-her2-positive/)
- targets: [HER2](https://onco.cc/targets/her2/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Zanidatamab](https://onco.cc/drugs/zanidatamab/)
- trials: [DESTINY-Gastric04](https://onco.cc/trials/destiny-gastric04/), [HERIZON-GEA-01](https://onco.cc/trials/herizon-gea-01/), [ToGA](https://onco.cc/trials/toga/)

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