Abstract
Nivolumab plus ipilimumab achieves higher response rates than previously reported for nivolumab alone.
Major finding: Nivolumab plus ipilimumab achieves higher response rates than previously reported for nivolumab alone.
Approach: The phase II CheckMate-142 trial evaluated nivolumab plus ipilimumab in dMMR/MSI-H colorectal cancer.
Impact: Nivolumab plus ipilimumab may be more effective than nivolumab alone in dMMR/MSI-H colorectal cancer.
In patients with metastatic colorectal cancer, those with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) tumors have poorer outcomes and derive less benefit from conventional chemotherapy. However, these patients also demonstrate better responses to immune checkpoint blockade with the anti–PD-1 antibody nivolumab, and it has been previously reported that nivolumab achieves a 31% overall response rate in these patients. In patients with metastatic melanoma, treatment with the anti-CTLA4 antibody ipilimumab plus nivolumab achieved better responses than nivolumab alone, and preclinical studies have demonstrated that ipilimumab can enhance the efficacy of nivolumab. Thus, Overman and colleagues evaluated the safety and efficacy of nivolumab plus ipilimumab in 119 patients with previously treated metastatic dMMR/MSI-H tumors as part of the multicenter, open-label, phase II CheckMate-142 trial. The primary endpoint was overall response rate, and other endpoints included safety, tolerability, progression-free survival, and overall survival. The overall response rate was 55%, with complete responses occurring in 4 (3%) patients and partial responses occurring in 61 (51%) patients. The 12-month progression-free and overall survival rates were 71% and 85%, respectively. Nivolumab plus ipilimumab exhibited a manageable toxicity, with treatment-related grade 3–4 adverse events occurring in 32% of patients. Thirteen percent of patients discontinued treatment due to drug-related adverse events. Taken together, the results of this phase II trial indicate that nivolumab plus ipilimumab achieves high response rates with a manageable safety profile in patients with dMMR/MSI-H metastatic colorectal cancer. Based on indirect comparison with nivolumab alone, combined therapy with nivolumab plus ipilimumab improves therapeutic efficacy, supporting further investigation of this combination in patients with dMMR/MSI-H tumors.
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