Nivolumab plus ipilimumab shows clinical benefit as first-line treatment for centrally confirmed MSI-H/dMMR mCRC

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Published: 2 Jun 2024
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Prof Heinz-Josef Lenz - Keck School of Medicine of USC, Los Angeles, USA

Prof Heinz-Josef Lenz speaks to ecancer at ASCO 2024 about the expanded efficacy analysis from CheckMate 8HW.

This study evaluates nivolumab plus ipilimumab versus chemotherapy as first-line treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer.

In the previous analysis, nivolumab plus ipilimumab demonstrated superior progression-free survival versus chemotherapy.

Prof Lenz reports that the clinical benefit with first line nivolumab plus ipilimumab versus chemotherapy was maintained after subsequent therapy, as shown by improved progression-free survival 2 in patients with centrally confirmed MSI-H/dMMR mCRC.

Nivolumab plus ipilimumab shows clinical benefit as first-line treatment for centrally confirmed MSI-H/dMMR mCRC

Prof Heinz-Josef Lenz - Keck School of Medicine of USC, Los Angeles, USA

I’m here to present our data on the expanded efficacy analysis of CheckMate 8HW. 8HW is a randomised phase III clinical trial testing the efficacy of nivolumab versus nivolumab/ipilimumab versus chemotherapy. We are presenting today the data on the first-line treatment with mismatch repair deficient colon cancer treated with nivolumab/ipilimumab versus chemotherapy. The initial study showed, and was earlier presented at ASCO GI, that the study met its primary endpoint by improving, an unprecedented improvement of progression free survival compared to chemotherapy with a hazard ratio of 0.21. 

The expanded efficacy analysis actually focussed on PFS2 which is defined as the time from randomisation until progression of the subsequent treatment or the initiation of the second subsequent treatment or death. PFS2 is important because in order to better understand the impact of subsequent treatment on efficacy outcome. The data for PFS2 show that it really also favours nivolumab/ipilimumab, despite the fact that in the chemotherapy arm 67% crossed over to immunotherapy, 46% to nivolumab/ipilimumab and 20% to a non-study immunotherapy.

The hazard ratio of the PFS2 for nivolumab/ipilimumab was 0.27, so a 73% reduction of risk of death or cancer progression. The median of PFS2 for nivolumab/ipilimumab was not reached, for chemotherapy it was 29.9 months. The two-year PFS2 rate was 83% for nivolumab/ipilimumab and 52% for chemotherapy. This data indicates that nivolumab/ipilimumab is a treatment as a standard of care treatment option for first-line mismatch repair deficient colorectal cancer and that the benefit maintains through subsequent therapies.

What could be the impact of this research?

We had already data on CheckMate 142 showing nivolumab/ipilimumab being highly effective in MSI high mismatch repair deficient colon cancer compared to the approval of pembrolizumab as a single immunotherapy agent. This data indicates that the combination may be more effective. The direct comparison between nivolumab and ipilimumab and nivolumab is not mature enough but this data further confirm the high efficacy of the combination of ipilimumab and nivolumab in first line.

What is interesting is that only patients with mismatch repair deficient tumours were eligible and by local testing. When it was centrally confirmed about 15% in the nivolumab/ipilimumab and 13% in the chemotherapy arm were essentially confirmed. So there is between 10-15% issues with the local testing which did not confer for MSI high which raises concerns that patients may not receive the appropriate treatment. So it is very important to make sure you will talk to your testing, either laboratory or to your pathologist or the one lab you work with, to make sure you have accurate testing technology.

You’re welcome.