Immunotherapy for the Treatment of Gastrointestinal Cancer
Summary of Recommendations
- For all patients with a 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. MMR status may be obtained by IHC.
- TMB testing should be performed on tumor tissue. At the time of guideline writing, TMB assessment using ctDNA is strictly investigational and may overestimate mutational load (LE:4).
- At the time of guideline writing, PD-L1 expression is not a validated biomarker of response to ICIs for GI cancers outside of esophagogastric cancers (LE:3).
- For all patients with advanced GI cancer, tumor tissue evaluation by NGS is recommended, if feasible. NGS testing is particularly encouraged for tumors known to have actionable mutations or when results may determine clinical trial eligibility.
- All patients with esophagogastric cancers should undergo tumor testing for PD-L1 expression (LE:2) and MSI-H/dMMR status (LE:3). TMB (LE:3) should also be considered. For patients with esophagogastric adenocarcinomas, tumor tissue should also be tested for HER2 expression (LE:2).
- For patients with esophagogastric cancers, PD-L1 expression testing should be performed using a validated antibody. At the time of writing, the 22C3 and 28-8 antibodies are both validated.
- For patients with esophagogastric adenocarcinoma, CPS is the most established scoring system used to quantify PD-L1 expression (LE:2). For ESCC, both CPS and TPS are valid approaches to determine eligibility for ICI therapy (LE:2).
- For patients with esophagogastric cancers, routine EBV testing is not currently recommended for ICI treatment determination.
- For all patients with resectable esophagogastric cancers, clinical trial enrollment should be considered at all stages of treatment, when feasible.
- For patients with resected (R0) stage II or III esophageal or GEJ cancers who received neoadjuvant CRT and have residual pathological disease, adjuvant nivolumab is a SOC option (LE:2).
- For all patients with advanced esophagogastric cancers, clinical trial enrollment should be considered at all stages of treatment, when feasible.
- For patients with untreated, advanced, MSS/pMMR esophagogastric cancers, single-agent ICIs are not recommended. Single-agent anti-PD-1 therapy may be an option for patients with untreated, advanced, MSI-H/dMMR esophagogastric cancers who are not eligible for chemotherapy (LE:3).
- For patients with untreated, advanced, TPS ≥1 ESCC, nivolumab in combination with fluoropyrimidine-based and platinum-based chemotherapy is a preferred SOC option (LE:2).
- For patients with untreated, advanced, CPS ≥10 ESCC, chemotherapy plus pembrolizumab is a preferred SOC option (LE:2).
- For patients with untreated, advanced, TPS ≥1 ESCC, nivolumab in combination with ipilimumab is also an approved option (LE:2).
- For patients with untreated, advanced, CPS ≥10, HER2-negative esophageal or Siewert type I GEJ adenocarcinoma, chemotherapy plus pembrolizumab is a SOC option (LE:2).
- For patients with untreated, advanced, HER2-negative esophageal/GEJ/gastric adenocarcinomas with CPS ≥5 or that are MSI-H/dMMR, chemotherapy plus nivolumab is a SOC option (LE:2).
- For patients with untreated, HER2-positive, advanced esophagogastric adenocarcinoma, chemotherapy plus trastuzumab plus pembrolizumab is recommended (LE:2).
- For all patients with SBA, PDAC, and BTC, clinical trial enrollment should be considered at all stages of treatment, when feasible.
- For patients with previously treated, advanced MSI-H/dMMR SBA, PDAC, or BTC, pembrolizumab monotherapy is a recommended treatment option (LE:3) and dostarlimab monotherapy is a recommended treatment option for dMMR tumors only (LE:3).
- For patients with previously treated TMB-H (≥10 mut/Mb) SBA, PDAC, or BTC, anti-PD-1 ICI monotherapy may be considered if no other treatment options are available (LE:3); however, at the time of guideline publication, there were insufficient data on efficacy in these tumor types.
- For patients with MSS/pMMR, TMB-L (<10 mut/Mb) SBA or PDAC, ICIs should not be used outside of a clinical trial (LE:3).
- For patients with untreated, advanced BTC, treatment with combination gemcitabine/cisplatin/durvalumab (LE:2) is recommended (LE:2) unless a contraindication to immunotherapy exists.
- For patients with treatment-refractory, immunotherapy-naïve, advanced MSS/pMMR BTC, treatment with combination lenvatinib plus pembrolizumab (LE:3) or nivolumab with (LE:3) or without (LE:3) ipilimumab may be considered if a suitable clinical trial is not available.
- All patients with metastatic CRC should have tumor tissue evaluated by NGS.
- For all patients with CRC and SCCA, PD-L1 expression does not currently inform treatment decisions for ICIs.
- For patients with CRC, MSI/MMR status (LE:2) and a POLE/POLD1 mutation with an associated ultramutated TMB (LE:3) are the primary biomarkers that should be used to inform ICI treatment decisions.
- For all patients with CRC, clinical trial enrollment should be considered at all stages of treatment, when feasible.
- For patients with untreated, metastatic, MSI-H/dMMR CRC, pembrolizumab monotherapy is recommended (LE:2). Treatment with combination nivolumab plus ipilimumab may be considered for this indication as well (LE:3), although there are no randomized data to suggest that this regimen is superior to pembrolizumab monotherapy.
- For patients with untreated, metastatic, MSS/pMMR CRC, treatment with ICIs is not recommended outside of a clinical trial. This applies to patients with tumors that are TMB-H while being MSS/pMMR (LE:3), except for patients with POLE/POLD1 mutations with an associated ultramutated TMB (LE:3).
- For patients with previously treated, metastatic, MSI-H/dMMR CRC who have not received prior ICI therapy, pembrolizumab monotherapy (LE:3) or nivolumab with (LE:3) or without (LE:3) ipilimumab are all recommended options. Dostarlimab monotherapy is a recommended treatment option for dMMR disease only (LE:3).
- For patients with resected pathological stage I–III MSI-H/dMMR colon cancer, ICIs should not be used in the adjuvant setting outside of a clinical trial. A non-randomized multicenter study of neoadjuvant ICI therapy for patients with resectable dMMR colon cancer demonstrated a pCR (ypT0N0) in 67% of patients (LE:3), but longer follow-up is needed to address survival outcomes. Clinical trial participation is preferred.
- For patients with MSI-H/dMMR resectable rectal cancer, phase II data from a single group study of neoadjuvant ICI therapy suggest remarkable activity (LE:3), but longer follow-up is needed to address the DOR. Clinical trial participation is preferred.
- For all patients with SCCA, clinical trial enrollment should be considered at all stages of treatment, when feasible.
- For patients with treatment-naïve, metastatic SCCA with any MSI/MMR status and/or TMB, there are insufficient data to recommend first-line ICI therapy.
- For patients with previously treated, metastatic SCCA, nivolumab (LE:3) or pembrolizumab (LE:3) are recommended treatment options regardless of MSI/MMR, TMB, and PD-L1 status.
- Patient and caregiver education should include a focused discussion of the fundamental differences between immunotherapy, targeted therapy, and chemotherapy tailored to the patient’s learning style. Patient education should include an extensive discussion of irAEs.
- Providers should initiate a conversation about the cost associated with ICIs and cancer care early and address financial hardship throughout the course of care.
- Realistic expectations and goals of treatment should be discussed at the time of diagnosis and at times of changes in clinical status for all patients with GI cancer.
- Providers should advise their patients to promptly report all medication changes to their oncology team as several medications, particularly steroids (LE:4), may impact the efficacy of immunotherapy.
Recommendation Grading
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Overview
Title
Immunotherapy for the Treatment of Gastrointestinal Cancer
Authoring Organization
Society for Immunotherapy of Cancer
Publication Month/Year
June 7, 2023
Last Updated Month/Year
August 8, 2023
Supplemental Implementation Tools
Document Type
Guideline
Country of Publication
US
Document Objectives
Gastrointestinal (GI) cancers, including esophageal, gastroesophageal junction, gastric, duodenal and distal small bowel, biliary tract, pancreatic, colon, rectal, and anal cancer, comprise a heterogeneous group of malignancies that impose a significant global burden. Immunotherapy has transformed the treatment landscape for several GI cancers, offering some patients durable responses and prolonged survival. Specifically, immune checkpoint inhibitors (ICIs) directed against programmed cell death protein 1 (PD-1), either as monotherapies or in combination regimens, have gained tissue site-specific regulatory approvals for the treatment of metastatic disease and in the resectable setting. Indications for ICIs in GI cancer, however, have differing biomarker and histology requirements depending on the anatomic site of origin. Furthermore, ICIs are associated with unique toxicity profiles compared with other systemic treatments that have long been the mainstay for GI cancer, such as chemotherapy. With the goal of improving patient care by providing guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of GI cancer. Drawing from published data and clinical experience, the expert panel developed evidence- and consensus-based recommendations for healthcare professionals using ICIs to treat GI cancers, with topics including biomarker testing, therapy selection, and patient education and quality of life considerations, among others.
Inclusion Criteria
Male, Female, Adult, Older adult
Health Care Settings
Ambulatory, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Treatment, Management
Diseases/Conditions (MeSH)
D007167 - Immunotherapy, D005770 - Gastrointestinal Neoplasms
Keywords
immunotherapy, Cancer immunotherapy, gastrointestinal cancer, gastrointestinal neoplasms
Source Citation
Kelly RJ, Bever K, Chao J, Ciombor KK, Eng C, Fakih M, Goyal L, Hubbard J, Iyer R, Kemberling HT, Krishnamurthi S, Ku G, Mordecai MM, Morris VK 2nd, Paulson AS, Peterson V, Shah MA, Le DT. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer. J Immunother Cancer. 2023 Jun;11(6):e006658. doi: 10.1136/jitc-2022-006658. PMID: 37286304; PMCID: PMC10254964.