Multinational phase 3 trial of nivolumab plus ipilimumab for MSI-H or dMMR metastatic colorectal cancer

Patients with microsatellit-instability-High (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. The multinational phase 3 CheckMate & HW trial evaluated the combination of nivolumab plus ipilimumab versus chemotherapy for these patients. Interim analysis of patients who had not received previous systemic therapy for metastatic disease found that the progression-free survival outcomes were significantly (p<0.001) better with nivolumab plus ipilimumab than with chemotherapy: 24-month PFS rate 72% versus 14%. At 24 months, the restricted mean survival time was 10.6 months longer with nivolumab plus ipilimumab than with chemotherapy. Grade 3 or 4 treatment-related adverse events occurred in 23% of the patients in the nivolumab-plus-ipilimumab group and in 48% of the patients in the chemotherapy group. The authors conclude that PFS was longer with nivolumab plus ipilimumab than with chemotherapy among patients who had not previously received systemic treatment for MSI-H or dMMR metastatic colorectal cancer.