Dual vs Single Immune Checkpoint Inhibitors in MSI-H/dMMR mCRC: ESMO Gastrointestinal Oncology | September 2026

Introduction:

Immune checkpoint inhibitors (ICIs) are the standard first-line treatment for MSI-H/dMMR metastatic colorectal cancer (mCRC). In the absence of direct head-to-head trials, this reconstructed individual patient data (IPD) analysis compared nivolumab–ipilimumab, nivolumab, and pembrolizumab using data from CheckMate 8HW and KEYNOTE-177.

Why was this study needed?

• No randomized trial has directly compared nivolumab–ipilimumab with pembrolizumab.
• Dual ICI therapy has recently emerged as a new treatment option.
• Clinicians need comparative data to guide first-line treatment selection.
• Reconstructed individual patient data provide a practical method for indirect treatment comparisons.
• Safety differences between dual- and single-agent immunotherapy remain clinically important.

Results:

• Dual immunotherapy with nivolumab–ipilimumab demonstrated superior estimated progression-free survival compared with pembrolizumab, suggesting greater disease control in MSI-H/dMMR metastatic colorectal cancer.
• Single-agent nivolumab and pembrolizumab showed comparable progression-free survival, indicating similar efficacy between PD-1 inhibitor monotherapies.
• Dual immunotherapy resulted in significantly more grade 3–4 immune-related adverse events than nivolumab alone, highlighting the trade-off between improved efficacy and increased toxicity.

Clinical Impact:

This indirect comparison suggests that nivolumab–ipilimumab may become the preferred option for medically fit patients requiring maximal disease control, whereas single-agent pembrolizumab or nivolumab remain excellent choices for patients where safety and tolerability are priorities. These findings should be interpreted cautiously because they are based on reconstructed patient data rather than a direct randomized comparison.

Bottom Line:

Dual immune checkpoint blockade may provide longer progression-free survival than pembrolizumab in MSI-H/dMMR metastatic colorectal cancer, but at the cost of increased immune-related toxicity. Pembrolizumab and nivolumab appear to offer similar efficacy as single-agent PD-1 inhibitors, making treatment selection a balance between efficacy, toxicity, and patient preference.