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Cancers & treatments·Sequencing

HER2-positive gastric cancer: lines of therapy

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4 standard-of-care settings across 4 lines and 2 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

LineAll comersHER2
Early / localised·1
Advanced, first line1·
Second line1·
Third line and beyond·1

Early / localised

SubgroupSettingApproachProducts and trialsEvidence
HER2Localised diseasePerioperative FLOT and gastrectomy as for HER2-negative disease; adding HER2 therapy before surgery is unproven.
FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)Gastrectomy
75

Advanced, first line

SubgroupSettingApproachProducts and trialsEvidence
All comersAdvanced, first lineTrastuzumab with a platinum and a fluoropyrimidine (ToGA), plus pembrolizumab when PD-L1 CPS is 1 or above (KEYNOTE-811).
ToGATrastuzumabPembrolizumabCisplatinOxaliplatinCapecitabineFluorouracil (5-FU)HER2HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd
98

Second line

SubgroupSettingApproachProducts and trialsEvidence
All comersSecond lineTrastuzumab deruxtecan (DESTINY-Gastric01 and DESTINY-Gastric04); ramucirumab with paclitaxel where the conjugate is unavailable.
Trastuzumab deruxtecanDESTINY-Gastric04RamucirumabPaclitaxel / nab-paclitaxel
97

Third line and beyond

SubgroupSettingApproachProducts and trialsEvidence
HER2Later linesTrifluridine-tipiracil; trials of zanidatamab and other HER2 agents.
Trifluridine/tipiracilZanidatamabHERIZON-GEA-01
89

Sequence and caution pairings

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

For HER2-positive stomach cancer, an antibody-plus-chemotherapy first, then Enhertu when it progresses. Both steps now have phase 3 proof.

CautionApproved
Caution: DXd ADC + agents with pneumonitis risk

Enhertu and its DXd cousins can inflame the lungs; combining them with immunotherapy, radiation, or mTOR inhibitors stacks that risk.

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.