Treatment of Microsatellite Instability-High (MSI-H) Colorectal Cancer

Efficacy and Approval Status

The 2024 Chinese Society of Clinical Oncology (CSCO) Guidelines recommend nivolumab combined with ipilimumab for the treatment of MSI-H/dMMR advanced colorectal cancer in the first-, second-, and third-line settings (Grade 3 recommendation) 1, 2

PD-1/PD-L1 inhibitors are strongly recommended for patients with MSI-H/dMMR tumors (Level of Evidence: III, Grade of Recommendation: A) 3
First-line treatment options for MSI-H/dMMR metastatic colorectal cancer include nivolumab plus ipilimumab combination, with a significant improvement in progression-free survival compared to chemotherapy (HR, 0.21) 5
The phase III KEYNOTE-177 study demonstrated that pembrolizumab significantly improved progression-free survival compared to chemotherapy (16.5 vs 8.2 months; HR, 0.60) in first-line treatment of MSI-H/dMMR metastatic colorectal cancer 6

Common immune-mediated side effects affect the skin, liver, kidneys, gastrointestinal tract, lungs, and endocrine systems 5
Pneumonitis is one of the most serious side effects, occurring in approximately 3-7% of patients on checkpoint inhibitor therapy 5

Testing for MSI/MMR status should be performed before or during standard treatment of advanced solid tumors to determine eligibility for immunotherapy 7
When considering ipilimumab plus nivolumab for patients not appropriate for intensive therapy, be aware that this is a category 2B recommendation due to potential toxicity concerns 6