Guideline Video

Guideline Resources

  • Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer
  • American Society of Clinical Oncology
  • February 26th, 2026
  • Summary
  • Full-text

Video Transcription

Just published February 26th, 2026, the American Society of Clinical Oncology’s newest guideline on Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer.

The purpose of this guideline is to provide updated recommendations for immunotherapy and targeted therapy for patients with advanced gastroesophageal cancer. For the full guideline, make sure to check it out on guidelinecentral.com. Let’s get started. 

Starting on the section on Predictive biomarker testing

  • 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 esophageal squamous cell carcinoma, or 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. 

On to the section on First-line therapy

  • 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. 

For the section on Second- or third-line therapy

  • 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. 

And there you have it. Make sure to check out the full guideline from the American Society of Clinical Oncology and other related clinical decision support tools at guidelinecentral.com.

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