ASCO 2025 | CheckMate 8HW: expanded analysis of nivolumab & ipilimumab in MSI-H/dMMR mCRC

We presented this year at ASCO the expanded analysis of CheckMate 8HW. We have now a longer follow-up of 47 months, looking at the comparison of nivo-ipi versus chemo and nivo-ipi versus Nivolumab alone. CheckMate was a randomized phase three study. 839 patients were randomized to nivo alone, nivo-ipi, or chemotherapy by investigator choice. Patients with metastatic colon cancer with local testing for mismatch repair deficiency were eligible for this study. There were two dual endpoints. One for PFS comparing nivo-ipi with chemo, and the second PFS nivo-ipi versus nivo in patients who had centralized confirmed mismatch repair deficiency. The first part of the results was looking at longer follow-up of nivo-ipi versus chemo and the data showed that the median progression-free survival for nivo-ipi was 54.1 months compared to chemo was 5.9 months with a hazard ratio of 0.21. So, a 79% reduction of risk of progression or death, indicating that nivo-ipi continues to show an unprecedented improvement of progression-free survival in this patient population compared to chemotherapy alone. The second update is PFS2, which is defined as the disease progression of subsequent treatment as well as the start of the second subsequent treatment or death. This was also in favor of nivo-ipi with a hazard ratio of 0.28 indicating that sequence of treatment is very important. Indicating that when you have an MSI high tumor you should start with immunotherapy with nivo-ipi because subsequent treatments show more sensitivity even when you would do it the other way around. Now, PFS2 is very important because the chemotherapy patients got 71% immunotherapy. So this is very important to fully understand. We also updated the results on the comparison of nivo-ipi versus Nivo, and that showed a continued favor of nivo-ipi with a hazard ratio of 0.62. And PFS2 in this patient population had also a favor of nivo-ipi with a hazard ratio of 0.57. All these data suggest that nivo-ipiis a new treatment option and standard of care for patients with MSI high metastatic colorectal cancer. We also interestingly looked at the side effect profile to see if patients who have grade 3, 4 toxicity do better or worse. And the matter of fact is they do as well as the cohort numerically a little bit better. The response rate was 77 percent and the progression-free survival was also higher with the three years progression-free survival of 74% overall cohort was 67%. So we know that nivo-ipihas a higher response rate of 71 versus 58 and this seems to be explained when we plot PFS by best response that the improved benefit comes from the higher response rate. We also saw that most of the treatment-related adverse events come in the first six months. The frequency in both groups of Nivo and nivo-ipi are very similar with two exceptions. One is skin toxicity and one is endocrine side effects. But overall, the safety profile was very manageable and consistent with the safety profile of each component. So, we think this data further supports evidence that nivo-ipi should be the new standard of care for first-line metastatic colon cancer, which is microsatellite-unstable.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.