Guideline Video

Guideline Resources

  • Title: Immunotherapy for the Treatment of Gastrointestinal Cancer 
  • Society: Society for Immunotherapy of Cancer (SITC)
  • Publish Date: May 28, 2025
  • Guideline Summary
  • Full-text

Video Transcription

In today’s rapid update, we’ll be going over the Society for Immunotherapy of Cancer (SITC)’s newest update on Immunotherapy for the Treatment of Gastrointestinal Cancer. These guidelines were originally published in 2023, but underwent a focused update on May 28th, 2025.

In today’s video, we’ll just be going over key changes so to get the full recommendations including FDA approvals for new or expanded indications, make sure to check it out on guidelines central dot com. 

We’ll start off with the tissue-agnostic indications for immunotherapy in the treatment of GI cancer, specifically in the DNA polymerase epsilon and delta (POLE/POLD1) section:

  • For all patients with GI cancer, MSI/MMR status and TMB testing (for MSS/pMMR tumors) should be performed on tumor tissue in a CLIA-certified lab (LE:3). MSI status and TMB may be obtained by NGS. MSI can also be determined by PCR. MMR status may be obtained by IHC.

Next, we’ll take a look at new and updated recommendations that were added in the
esophageal/gastroesophageal junction/gastric cancer section:

  • For patients with gastric or GEJ adenocarcinoma, CLDN 18.2 testing should be performed using a validated antibody (LE:2).”
  • For patients with resectable gastric/GEJ adenocarcinoma that is dMMR/MSI-H, pre-operative ICIs should be considered in consultation with a multidisciplinary team (LE:2).
  • For patients with unresectable or metastatic ESCC following prior systemic chemotherapy that did not include a PD-1/PD-L1 inhibitor, tislelizumab is recommended (LE:2).
  • For patients with untreated, locally advanced unresectable or metastatic, HER2-negative, PD-L1 ≥1 gastric or GEJ adenocarcinoma, nivolumab, pembrolizumab, or tislelizumab with fluoropyrimidine- and platinum-containing chemotherapy is recommended (LE:2). For patients with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or GEJ adenocarcinoma, zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy is recommended (LE:2). There are no comparative data regarding the efficacy of zolbetuximab plus chemotherapy versus an ICI plus chemotherapy where both zolbetuximab and ICI therapy are indicated.
  • For patients with untreated, PD-L1 CPS ≥1, HER2-positive, advanced esophagogastric adenocarcinoma, chemotherapy plus trastuzumab plus pembrolizumab is recommended (LE:2).

Now on to the biliary tract cancers section, where we find two updated recommendations:

  • For patients with untreated, advanced BTC, treatment with combination gemcitabine and cisplatin with durvalumab (LE:2) or pembrolizumab (LE:2) is recommended unless a contraindication to immunotherapy exists.
  • For patients with treatment-refractory, immunotherapy-naïve, advanced MSS/pMMR BTC, treatment with a clinical trial is preferred but the following are considered suitable if a trial is not available: a) lenvatinib plus pembrolizumab (LE:3) or nivolumab (LE:3), b) nivolumab plus ipilimumab (LE:3), or c) nivolumab (LE:3) or pembrolizumab (LE:3).

Finally, we’ll cover two additional updated recommendations for colorectal and anal cancers

  • For patients with untreated, metastatic, MSI-H/dMMR CRC, pembrolizumab monotherapy (LE:2) or nivolumab plus ipilimumab (LE:2) are treatment options.
  • The final recommendation..  For patients with MSI-H/dMMR resectable rectal cancer, phase II data from a single-center study of neoadjuvant ICI therapy suggest remarkable activity (LE:3). ICI as neoadjuvant or definitive therapy with non-operative management in consultation with a multidisciplinary team can be considered, but clinical trial participation is preferred.

Make sure to check out the full guideline from The Society for Immunotherapy of Cancer and other related clinical decision support tools at guidelinecentral.com.

Copyright © 2025 Guideline Central, all rights reserved.