CheckMate 8HW

Arguably one of the most anticipated studies presented at ASCO GI 2025 consists of the randomized, phase III CheckMate 8HW study, comparing nivolumab (nivo) with or without ipilimumab (ipi) to standard of care chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability high, mismatch repair deficient (MSI-h/dMMR).¹ Previously, this trial demonstrated superiority of nivo monotherapy over chemotherapy. During ASCO GI 2025, the long-awaited results of the comparison between nivo monotherapy and nivo-ipi were presented. In this video, Prof Thierry André, medical oncologist at the Sorbonne University in Paris, and Prof Em Eric Van Cutsem, digestive oncologist at the University Hospitals Leuven, discuss the key take home messages from this presentation.

CheckMate 8HW was a 3-arm study in which patients with MSI-H/dMMR mCRC were randomly assigned to nivolumab (240 mg q2w for 6 doses, 480 mg q4w thereafter) (N= 353), nivo + ipi (240mg nivo + 1 mg/kg ipi q3w for 4 doses, nivo 480 mg q4w thereafter), or (N= 354) investigator’s choice of chemotherapy (mFOLOX, of FOLFIRI +/- cetuximab or bevacizumab) (N= 132). In total, 57% of patients in the study received the study drug in first line.

Nivo+ipi proved to be associated with a significantly better progression-free survival (PFS) than nivo alone, with a median PFS that was not reached for nivo+ipi as compared to 39.3 months for nivo alone (HR[95%CI]: 0.62[0.48-0.81]; p= 0.0003). At three years, this translated into a PFS rate of 68% for nivo+ipi as compared to 51% with nivo alone. The addition of ipi to nivo also led to a significantly higher response rate than what was seen with nivo alone (71% vs. 58%). 

Despite the slightly higher rate of adverse events seen with nivo+ipi, Prof André is convinced that these data mark nivo+ipi as the new standard of care for patients with MSI-H/dMMR mCRC. Only for patients with an active auto-immune disorder he would be reluctant to opt for the combination and rather go for an immune checkpoint inhibitor (ICI) in monotherapy. An important question for the years to come relates to the treatment of MSI-H/dMMR mCRC patients who progress on ICI monotherapy in first line. Are these patients still a candidate for nivo+ipi, or not? Several studies addressing this question are currently ongoing.