Gastric, Gastroesophageal Junction (GEJ) and Esophageal Adenocarcinoma

Authored by Yelena Y. Janjigian, published on 2026-04-30 01:33:31.0

Treatment algorithm for Gastric, Gastroesophageal Junction (GEJ) and Esophageal Adenocarcinoma by Yelena Y. Janjigian, MD, FASCO, Chief, Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center.

Gastric / GEJ / Esophageal Adenocarcinoma
- Stage I
  - Consider EUS to confirm Tis–T1b
    - Endoscopic Resection +/- Ablation
- Stage II / III
  - Consider diagnostic laparoscopy to confirm no occult peritoneal disease
    - Perioperative Therapy
      - Neoadjuvant
        
        FLOT + Durvalumab (FLOT-D)* Chemotherapy (FLOT) Chemoradiation (Carbo/Taxol + RT) *Preferred regardless of PD-L1 + or -
        
        Surgery
        
        Adjuvant
        
        FLOT + Durvalumab (FLOT-D) with Maintenance Durvalumab x 10 doses Chemotherapy Nivolumab in select cases
- Stage IV
  - Her2- / CLDN 18.2- / PD-L1- (CPS<1)
    - FOLFOX + Nivolumab*
      
      If can’t get a-PD1 → FOLFOX, Capox, or 5FU + Cisplatin If CLDN+ consider adding Zolbetuximab *Preferred regardless of PD-L1 + or -
      - Ramucirumab + Paclitaxel OR Doublet chemotherapy
        
        Carbo / Irinotecan Carboplatin / Paclitaxel 5FU / Cisplatin
        
        Chemotherapy: Single agent or Doublet
  - Her2- / CLDN 18.2- / PD-L1+ (CPS≥1)
    - FOLFOX + Nivolumab*
      
      If can’t get a-PD1 → FOLFOX, Capox, or 5FU + Cisplatin If CLDN+ consider adding Zolbetuximab *Preferred regardless of PD-L1 + or -
      - Ramucirumab + Paclitaxel OR Doublet chemotherapy
        
        Carbo / Irinotecan Carboplatin / Paclitaxel 5FU / Cisplatin
        
        Chemotherapy: Single agent or Doublet
  - CLDN 18.2+
    - FOLFOX + Zolbetuximab
      - Trastuzumab Deruxtecan (TDXD)
        
        Alternatively: Chemo + Zanidatamab ± anti-PD-1 based on HERIZON-01 data
        
        Clinical Trial
      - Clinical Trial
        
        Clinical Trial
  - HER2+
    - FOLFOX + Pembrolizumab + Trastuzumab
      - Trastuzumab Deruxtecan (TDXD)
        
        Alternatively: Chemo + Zanidatamab ± anti-PD-1 based on HERIZON-01 data
        
        Clinical Trial
      - Clinical Trial
        
        Clinical Trial
If dMMR/MSI-H (~10% of cases), perioperative immune checkpoint inhibition can be given without chemotherapy

tos privacy NCCN Gastric Cancer Guidelines ESMO Living Guideline: Gastric Cancer FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma FDA approves nivolumab for resected esophageal or GEJ cancer Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649 FDA Approves Zolbetuximab-clzb with Chemotherapy for Gastric or Gastroesophageal Junction Adenocarcinoma FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1)Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas