Nivolumab Plus Ipilimumab Combination for Microsatellite Instability-High, Mismatch Repair-Deficient Metastatic Colorectal Cancer
Results from CheckMate 8HW
Results from CheckMate 8HW
Thierry Andre, MD, Sorbonne University, Paris, France, discusses results from the CheckMate 8HW, presented at the 2025 ASCO Gastrointestinal Cancers Symposium. This trial evaluated the use of nivolumab plus ipilimumab compared with nivolumab monotherapy among patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer.
Dr Andre concluded, that these are "important results and probably a new standard of care in this population of patients."
Transcript:
I’m Thierry Andre, I am a medical oncologist in Paris, at Saint Antoine Hospital. It was an honor for me to present this year at ASCO GI the second primary end point of [CheckMate] 8HW.
The background is the therapy of metastatic colorectal cancer, MSI-high and dMMR. And this presentation was the third step. The first step was pembrolizumab, pembrolizumab demonstrated efficacy and was really a change of padding for the therapy of MSI-high metastatic colorectal cancer with the publication in New England [Journal of Medicine], it's now 5 years ago, with the efficacy of immunotherapy without chemo[therapy] for these patients with a hazard ratio at 0.61 comparing to chemo[therapy] or targeted therapy and the standard of care for this patient. It was after necessary to try to improve the things, and that’s why [CheckMate] 8HW was conducted.
[CheckMate] 8HW was a study for MSI-high/dMMR metastatic colorectal cancer. It is a study with 3 arms, randomization between nivo[lumab] plus ipilimumab versus nivolumab alone versus chemo[therapy] plus targeted therapy. I presented the next year the result of the comparison between nivolumab-ipilimumab versus chemo[therapy]. It was published 2 months ago in New England Journal of Medicine, and it was amazing result with a hazard ratio of 0.1 between the combination of nivolumab-ipilimumab versus chemo[therapy] in first line. It was amazing control of the disease at 2 years for metastatic disease, 71% with the combination.
At ASCO GI this year, it was the third step. The third step was the comparison between nivolumab plus ipilimumab versus nivolumab alone. It was very important because to try to demonstrate it as a new standard of care. And results are in a population, not only in first line, it is a mix, with first line as the majority, 52% first line, but also patients who are refractory to chemotherapy. And the second primary end point of this trial met its statistical significance. The combination improved the PFS: between nivo[lumab]-ipi[limumab] versus nivo[lumab] the hazard ratio is 0.61. The P-value is highly significant. Also, 71% of patient had control at 2 years, against 56% with nivo[lumab] alone. And overall response rate with combination at 71%, very high, compared to 58% with nivolumab alone.
A little more toxicity with the combination, but it is 22% vs 14% of grade 3/4 treatment-related adverse events. Treatment-related adverse events which led to treatment discontinuation, it's 14% for the combination and 6% for the monotherapy. Most immune-mediated adverse events were grade 1 and 2. Grade 3 and 4 occurred in less than 5% of the patients.
With all this data, it seems that the combination of nivolumab-ipilimumab is now the standard of care for these patients. Also because all the groups benefited from the combination, compared to the monotherapy.
One particular point about the diagnosis, because diagnosis of MSI-high/dMMR is very important. Because misdiagnosis is something relatively frequent. In this trial, it is 14%. The primary end point was on confirmed centrally MSI-high or dMMR. By central control, we found a 14% of patients misdiagnosed. It’s a special warning for the diagnostic. It's better to test immunochemistry and PCR, or NGS to be sure that the patient is dMMR or MSI-high. Because if you treat the patient with a misdiagnosed MSS/pMMR [microsatellite stable/mismatch repair proficient], it's really not good point for the patient because immunotherapy didn't work.
To conclude, the results of this trial were published the day of the meeting in Lancet Journal. And all the data are now online. It’s important results and probably a new standard of care in this population of patients. Thank you very much for your attention.
Source:
Andre T, Elez E, Lenz H-J, et al. First results of nivolumab (NIVO) plus ipilimumab (IPI) vs NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) from CheckMate 8HW. Presented at 2025 ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA. Abstract LBA143