Gastric, Gastroesophageal Junction (GEJ) and Esophageal Adenocarcinoma

Authored by Yelena Y. Janjigian, published on 2026-03-16 18:22:51.0

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.

  1. 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
            <p>FLOT + Durvalumab (FLOT-D)*<br>Chemotherapy (FLOT)<br>Chemoradiation (Carbo/Taxol + RT)</p><p>*Preferred regardless of PD-L1 + or -</p>
            • 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*
          <p>If can’t get a-PD1 → FOLFOX, Capox, or 5FU + Cisplatin<br>If CLDN+ consider adding Zolbetuximab</p><p>*Preferred regardless of PD-L1 + or -</p>
          • 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*
          <p>If can’t get a-PD1 → FOLFOX, Capox, or 5FU + Cisplatin<br>If CLDN+ consider adding Zolbetuximab</p><p>*Preferred regardless of PD-L1 + or -</p>
          • 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
  2. If dMMR/MSI-H (~10% of cases), perioperative immune checkpoint inhibition can be given without chemotherapy
tosprivacyNCCN Gastric Cancer GuidelinesESMO Living Guideline: Gastric CancerFDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinomaFDA approves nivolumab for resected esophageal or GEJ cancerNivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649FDA Approves Zolbetuximab-clzb with Chemotherapy for Gastric or Gastroesophageal Junction AdenocarcinomaFDA 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 trialFDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas