Treatment of dMMR/MSI-H Tumors

Introduction to dMMR/MSI-H Tumors

The American Society of Clinical Oncology recommends immunotherapy as the initial treatment for patients with dMMR/MSI-H tumors across multiple cancer types, with PD-1 inhibitors demonstrating superior outcomes compared to conventional chemotherapy 1, 2

Immunotherapy is strongly recommended as the initial approach for MSI-H or dMMR rectal cancers, with evidence quality: low and strength of recommendation: strong, according to the Journal of Clinical Oncology 1, 2
Dostarlimab achieved 100% clinical complete response rates in locally advanced rectal cancer, with all patients maintaining complete response with zero progression or recurrence at 2024 data analysis 3
No grade 3 or higher adverse events were reported with dostarlimab monotherapy in this population 3

The National Comprehensive Cancer Network recommends pembrolizumab, dostarlimab, or nivolumab as first-line therapy for metastatic dMMR/MSI-H colorectal cancer, with an objective response rate of 43.5% 3
Nivolumab plus fluoropyrimidine and oxaliplatin-based chemotherapy is recommended as first-line treatment for MSI-H gastric cancer, independent of PD-L1 status, with a median overall survival of 38.7 months versus 12.3 months with chemotherapy alone 7, 8, 9

Pembrolizumab monotherapy is a Category 2A preferred option for MSI-H tumors, with an ORR of 45.8% and median PFS of 11 months in previously treated MSI-H gastric cancer 9
Nivolumab plus ipilimumab is a Category 2A preferred option for first-line MSI-H disease, with median OS not reached versus 10 months with chemotherapy 8, 9

Adjuvant fluoropyrimidine-only chemotherapy is not routinely recommended for patients with dMMR or MSI tumors, as it provides no benefit and may cause harm, according to the Journal of Clinical Oncology 6
Oxaliplatin-containing chemotherapy may be considered for patients with dMMR or MSI who have T4 tumors and/or other high-risk features, excluding poor differentiation 6

Test all colorectal cancers for MMR/MSI status using immunohistochemistry or PCR, as recommended by the Praxis Medical Insights 3, 4
Offer dostarlimab, pembrolizumab, or nivolumab as initial therapy for locally advanced rectal cancer, and assess for clinical complete response at 6 months using MRI, PET/CT, endoscopy, DRE, and biopsy 3, 4
For metastatic disease, first-line options include dostarlimab, pembrolizumab, or nivolumab, with or without ipilimumab, and continue immunotherapy per FDA-approved duration 3, 9
For gastric cancer, preferred first-line treatment is nivolumab plus fluoropyrimidine and oxaliplatin, with alternative options including pembrolizumab monotherapy or nivolumab plus ipilimumab 7, 8, 9