Gastric & gastro-oesophageal junction cancer: lines of therapy

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15 standard-of-care settings across 6 lines and 2 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers	HER2
Screening, prevention and diagnosis	1	·
Early / localised	4	·
Advanced, first line	1	4
Second line	·	2
Third line and beyond	1	1
Other settings	1	·

Screening, prevention and diagnosis

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Prevention and screening	H. pylori eradication reduces incidence; endoscopic screening programmes in Japan and Korea (biennial from age 40-50) detect most cancers at a curable stage. No population screening in the West. Prophylactic total gastrectomy for germline CDH1 carriers.	Chemoprevention & risk-reducing surgeryGermline (hereditary) testing		91

Early / localised

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Localised	Perioperative FLOT ± durvalumab; D2 gastrectomy.	DurvalumabRobotic & minimally invasive surgery	NCCN Guidelines: Gastric Cancer	86
All comers	Early (T1a) disease	Endoscopic submucosal dissection for well-differentiated mucosal tumours ≤2 cm without ulceration (expanded criteria in Japan); otherwise gastrectomy.	Endoscopic resection (EMR / ESD)		40
All comers	Resectable stage II-III (Western)	Perioperative FLOT + durvalumab (MATTERHORN: OS HR 0.78, pCR 19%) with D2 gastrectomy; FOLFOX/CAPOX perioperatively for patients unfit for docetaxel.	MATTERHORNFLOT (5-FU, leucovorin, oxaliplatin, docetaxel)DurvalumabCAPOX (capecitabine, oxaliplatin)	NCCN · Category 1 (perioperative FLOT)	89
All comers	Resectable stage II-III (Asian practice)	D2 gastrectomy then adjuvant S-1 (ACTS-GC) or CAPOX (CLASSIC) for 6-12 months; neoadjuvant approaches increasingly adopted.	CAPOX (capecitabine, oxaliplatin)		78

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Advanced first line	Chemotherapy + PD-1 ± trastuzumab ± zolbetuximab by biomarker.	NivolumabPembrolizumabTrastuzumab	NCCN Guidelines: Gastric Cancer	98
HER2	Advanced, HER2-positive, first line	Trastuzumab + fluoropyrimidine/platinum + pembrolizumab (KEYNOTE-811, PD-L1 CPS ≥1); zanidatamab + chemotherapy ± tislelizumab after HERIZON-GEA-01 (PFS 12.4 vs 8.1 months; sBLA 2026).	ToGAHERIZON-GEA-01TrastuzumabZanidatamabPembrolizumabTislelizumabHER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd	NCCN · Category 1 (trastuzumab + chemo ± pembroliz…	98
HER2	Advanced, HER2-negative, PD-L1 CPS ≥5 (or ≥1), first line	Nivolumab (CheckMate 649) or pembrolizumab (KEYNOTE-859) or tislelizumab (RATIONALE-305) with FOLFOX or CAPOX; add zolbetuximab if CLDN18.2-positive (sequencing/combination under study).	CheckMate 649KEYNOTE-859NivolumabPembrolizumabTislelizumabFOLFOX (5-FU, leucovorin, oxaliplatin)CAPOX (capecitabine, oxaliplatin)	NCCN · Category 1 (CPS ≥5)ESMO-MCBS · 3 (nivolumab, CPS ≥5)	98
HER2	Advanced, CLDN18.2-positive (≥75%), HER2-negative, first line	Zolbetuximab + mFOLFOX6 or CAPOX (SPOTLIGHT/GLOW). PD-L1 CPS ≥5 double-positives: either add-on; combination trials ongoing.	SPOTLIGHT & GLOWZolbetuximabFOLFOX (5-FU, leucovorin, oxaliplatin)CAPOX (capecitabine, oxaliplatin)Biomarker-directed first-line quadruplets in gastric cancer	NCCN · Category 1	82
HER2	Advanced, HER2-negative, PD-L1 CPS <1 and CLDN18.2-negative	FOLFOX or CAPOX chemotherapy alone; MSI-high tumours get PD-1 blockade regardless of CPS.	FOLFOX (5-FU, leucovorin, oxaliplatin)CAPOX (capecitabine, oxaliplatin)Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)		82

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
HER2	Second line, HER2-positive	Trastuzumab deruxtecan 6.4 mg/kg (DESTINY-Gastric04, OS 14.7 vs 11.4 months) if HER2 persists on re-biopsy or ctDNA.	DESTINY-Gastric04Trastuzumab deruxtecan	NCCN · Category 1	97
HER2	Second line, HER2-negative	Ramucirumab + paclitaxel (RAINBOW, OS 9.6 vs 7.4 months); CLDN18.2-positive: sonesitatug vedotin after CLARITY-Gastric 01 (2026) or satri-cel CAR-T (China).	RAINBOWRamucirumabPaclitaxel / nab-paclitaxelCLARITY-Gastric 01Sonesitatug vedotinSatricabtagene autoleucelCLDN18.2 antibody first line → CLDN18.2 ADC or CAR-T on progression	NCCN · Category 1 (ramucirumab + paclitaxel)	94

Third line and beyond

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Third line and beyond	Trifluridine/tipiracil (TAGS, OS 5.7 vs 3.6 months); irinotecan; clinical trials (FGFR2b, CLDN18.2 bispecifics, T-cell engagers).	Trifluridine/tipiracil		89
HER2	Later lines	T-DXd (HER2+), zanidatamab, CLDN18.2 CAR-T/ADC in trials.	Trastuzumab deruxtecanZanidatamabSatricabtagene autoleucelSonesitatug vedotin	ESMO-MCBS · 2 (DESTINY-Gastric01 trastuzumab deruxtecan)	97

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Peritoneal metastases	Systemic therapy; intraperitoneal paclitaxel, HIPEC, and PIPAC in trials; palliative gastrectomy not recommended (REGATTA).	Peritoneal metastasisHIPEC / PIPAC (intraperitoneal chemotherapy)Peritoneal-directed therapy for gastric cancer		60

Sequence and caution pairings

SequenceApproved

CLDN18.2 antibody first line → CLDN18.2 ADC or CAR-T on progression

Hit Claudin 18.2 twice: first with a plain antibody plus chemotherapy, then with an ADC or engineered cells when the cancer comes back.

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.

Regimens in the library

mFOLFOX6 CAPOX FOLFIRI FLOT CROSS chemoradiation Nivolumab + FOLFOX or CAPOX Pembrolizumab + cisplatin + fluorouracil

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.