Around 4%-7% of patients with metastatic colorectal cancer have DNA repair defects, including high microsatellite instability (MSI-H) or mismatch repair-deficiency (dMMR).1,2 In the phase II CheckMate 142 study, nivolumab plus ipilimumab led to deep and durable responses and promising survival rates in patients with MSI-H or dMMR metastatic colorectal cancer.3,4 The CheckMate 8HW study is an ongoing, multinational phase III trial evaluating nivolumab plus ipilimumab in patients with MSI-H or dMMR metastatic colorectal cancer.5
METHODS
The open-label, phase III CheckMate 8HW study randomised patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive (2:2:1) nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The dual primary endpoints were progression-free survival (PFS) with nivolumab plus ipilimumab versus chemotherapy as first-line therapy, and PFS with nivolumab plus ipilimumab versus nivolumab alone in patients regardless of prior systemic therapy for metastatic disease. This prespecified interim analysis assessed PFS with nivolumab plus ipilimumab versus chemotherapy in the first-line setting.
RESULTS
A total of 303 patients with previously untreated metastatic disease were randomly assigned to receive nivolumab plus ipilimumab or chemotherapy. Of these patients, 255 had centrally confirmed MSI-H or dMMR tumours and were included in the efficacy analysis. After a median follow-up of 31.5 months, nivolumab plus ipilimumab significantly improved PFS compared to chemotherapy (2-year PFS: 72% versus 14%, 2-sided log-rank p< 0.001). At 24 months, the restricted mean survival benefit was 10.6 months longer with nivolumab plus ipilimumab versus chemotherapy (mean 19.2 months versus 8.6 months). The median treatment duration was 13.5 months with nivolumab plus ipilimumab versus 4.0 months with chemotherapy. Grade 3-4 adverse events occurred in 48% and 67% of patients treated with nivolumab plus ipilimumab and chemotherapy, respectively. Grade 3-4 treatment-related adverse events occurred in 23% and 48% of patients treated with nivolumab plus ipilimumab and chemotherapy, respectively.
CONCLUSIONS
Nivolumab plus ipilimumab significantly prolonged PFS compared to chemotherapy among patients who did not receive prior systemic treatment for MSI-H or dMMR metastatic colorectal cancer.
References
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