The American Society of Clinical Oncology (ASCO) released an update to their Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer guideline. The 2026 update replaces the previous 2023 version, which we compare the recommendations to in the table below. A new good practice statement regarding predictive biomarker testing was included in this update, along with the expansion of several sections on first- and second-line therapy for advanced gastroesophageal cancer. The recommendations included for first-line treatment were doubled from five up to ten and a recommendation on esophageal squamous cell carcinoma was added into the second-line section.
With 14 recommendations included in the 2026 update highlighted and compared to the previous version below, we’re helping you understand what’s new in the 2026 update. Refer to the full-text versions (linked below) for the most thorough explanation of the recommendations.
Guidelines Referenced
- Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer
- Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer
- Published: January 2023
- Full Text
Comparison of Recommendations
| Item | 2023 Guideline | 2026 Guideline |
|---|---|---|
| Predictive Biomarker Testing | N/A | Testing to determine the presence of predictive biomarkers PD-L1, dMMR/MSI-H, CLDN18.2, and HER2 in gastroesophageal adenocarcinoma is recommended, and PD-L1 and dMMR/MSI-H status should be tested for ESCC. Clinicians should consider broad-based NGS testing, which includes pan-tumor biomarkers. The results of predictive biomarker testing should be available as soon as possible to inform treatment decision making. |
| First-Line Therapy | For HER2-negative patients with gastric AC and PD-L1 CPS ≥ 5, first-line therapy with nivolumab in combination with fluoropyrimidine- and platinum-based CT is recommended. For HER2-negative patients with esophageal or GEJ AC, first-line therapy with nivolumab for patients with PD-L1 CPS ≥ 5, or pembrolizumab for PD-L1 CPS ≥ 10, in combination with fluoropyrimidine- and platinum-based CT is recommended. For patients with HER2-negative esophageal squamous cell carcinoma (ESCC) and PD-L1 CPS ≥ 10, pembrolizumab plus fluoropyrimidine- and platinum-based CT is recommended. For patients with HER2-negative ESCC, and PD-L1 TPS ≥ 1%, nivolumab plus fluoropyrimidine- and platinum-based CT or nivolumab plus ipilimumab is recommended. For patients with HER2-positive gastric or GEJ previously untreated, unresectable or metastatic AC, trastuzumab plus pembrolizumab is recommended, in combination with fluoropyrimidine- and oxaliplatin-based CT. | For patients with pMMR/MSS HER2-negative gastric/GEJ or esophageal adenocarcinoma with PD-L1 expression ≥1 and absence of CLDN18.2 expression, first-line therapy with fluoropyrimidine- and platinum-based chemotherapy in combination with immunotherapy may be recommended. For patients with pMMR/MSS HER2-negative gastric/GEJ adenocarcinoma with PD-L1 expression <1 and positive CLDN18.2 expression, fluoropyrimidine- and platinum-based chemotherapy combined with zolbetuximab should be offered. For patients with pMMR/MSS HER2-negative gastric/GEJ adenocarcinoma with PD-L1 expression ≥1, and CLDN18.2 expression positivity, fluoropyrimidine- and platinum-based chemotherapy combined with immunotherapy or zolbetuximab may be offered on a case-by-case basis. For patients with pMMR/MSS HER2-negative gastroesophageal adenocarcinoma, PD-L1 expression <1, and absence of CLDN18.2 expression, first-line therapy with fluoropyrimidine- and platinum-based chemotherapy should be offered. For patients with pMMR/MSS HER2-positive gastric/GEJ adenocarcinoma with PD-L1 expression ≥1, pembrolizumab plus trastuzumab should be offered, in combination with fluoropyrimidine- and oxaliplatin-based chemotherapy. For patients with pMMR/MSS HER2-positive gastric/GEJ adenocarcinoma with PD-L1 expression <1, trastuzumab should be offered in combination with fluoropyrimidine- and oxaliplatin-based chemotherapy. Immunotherapy in combination with fluoropyrimidine- and oxaliplatin-based chemotherapy may be offered. Immunotherapy alone is an additional treatment option that may be offered on a case-by-case basis. For patients with pMMR/MSS ESCC and PD-L1 expression ≥1, first-line therapy with immunotherapy in combination with fluoropyrimidine- and platinum-based chemotherapy or nivolumab plus ipilimumab may be offered. For patients with pMMR/MSS ESCC with PD-L1 expression <1, first-line therapy with fluoropyrimidine- and platinum-based chemotherapy may be offered. |
| Second- or Third-Line Therapy | For patients with advanced gastroesophageal or GEJ AC whose disease has progressed after first-line therapy, ramucirumab plus paclitaxel is recommended. For HER2-positive patients with gastric or GEJ AC who have progressed after first-line therapy, trastuzumab deruxtecan is recommended. | For patients with pMMR/MSS advanced gastroesophageal adenocarcinoma whose disease has progressed after first-line therapy, ramucirumab plus paclitaxel may be offered. For HER2-positive patients with gastric/GEJ adenocarcinoma and progressive disease after first-line therapy, trastuzumab deruxtecan should be offered. For patients with ESCC whose disease has progressed after first-line combination chemotherapy without immunotherapy and with PD-L1 ≥1, nivolumab or tislelizumab may be offered, and for patients with PD-L1 ≥10, pembrolizumab may be offered. |
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