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Implications of Recent Data from CheckMate-142 in CRC

Insights From: Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center; Tanios Bekaii-Saab, MD, Mayo Clinic
Published: Wednesday, Feb 07, 2018



Transcript: 

Tanios Bekaii-Saab, MD: At a very high level, we’ve already known that microsatellite instability determines a likelihood of a response to PD-1 inhibitors. We have 2 approvals, pembrolizumab and nivolumab, in this stage. At ASCO GI, we’ve heard updates about nivolumab in MSI-high patients, which seems very consistent with what we’d expect for this group of patients. Those responses occur in 30% to 40% of the patients, and many of the responses can come later. Some of these responses occur beyond 24 weeks, so stable disease can essentially transform into a PR and the PR can transform into a CR.

The other component of the presentation included—it was a separate presentation, but it was part of the same study—nivolumab plus ipilimumab, trying to understand the added benefit of CTLA-4 inhibitors to PD-1 inhibitors. We know that strategy has been looked at in melanoma, has been looked at in gastric cancer, and has been looked at in a number of different cancers. It does seem in colorectal cancer, like with other cancers, to add few more responders historically, at least when compared to a PD-1 inhibitor alone. So, there may be some benefit in doing this, even when we use 2 different doses of nivolumab and 2 different doses of ipilimumab.

The question that remains is, is this going to change the outcome for those patients? In all frankness, in my own clinic, I have patients on the single-agent PD-1 inhibitors who respond tremendously, and they respond for not just a few months but for a few years, and they will never need another agent. The question is, who are those patients who may need the added benefit of CTLA-4 inhibition, and how do we best study this?

At this point in time, I don’t think that these data will change how we practice in clinic. In other words, a patient with an MSI-high tumor remains, at this point of time, a candidate for either pembrolizumab or nivolumab. We have 2 sets of great data with nivolumab presented at ASCO GI. I think the role of ipilimumab in colorectal cancer would need to be explored further and is not yet ready for prime time in clinic.

Transcript Edited for Clarity 
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Transcript: 

Tanios Bekaii-Saab, MD: At a very high level, we’ve already known that microsatellite instability determines a likelihood of a response to PD-1 inhibitors. We have 2 approvals, pembrolizumab and nivolumab, in this stage. At ASCO GI, we’ve heard updates about nivolumab in MSI-high patients, which seems very consistent with what we’d expect for this group of patients. Those responses occur in 30% to 40% of the patients, and many of the responses can come later. Some of these responses occur beyond 24 weeks, so stable disease can essentially transform into a PR and the PR can transform into a CR.

The other component of the presentation included—it was a separate presentation, but it was part of the same study—nivolumab plus ipilimumab, trying to understand the added benefit of CTLA-4 inhibitors to PD-1 inhibitors. We know that strategy has been looked at in melanoma, has been looked at in gastric cancer, and has been looked at in a number of different cancers. It does seem in colorectal cancer, like with other cancers, to add few more responders historically, at least when compared to a PD-1 inhibitor alone. So, there may be some benefit in doing this, even when we use 2 different doses of nivolumab and 2 different doses of ipilimumab.

The question that remains is, is this going to change the outcome for those patients? In all frankness, in my own clinic, I have patients on the single-agent PD-1 inhibitors who respond tremendously, and they respond for not just a few months but for a few years, and they will never need another agent. The question is, who are those patients who may need the added benefit of CTLA-4 inhibition, and how do we best study this?

At this point in time, I don’t think that these data will change how we practice in clinic. In other words, a patient with an MSI-high tumor remains, at this point of time, a candidate for either pembrolizumab or nivolumab. We have 2 sets of great data with nivolumab presented at ASCO GI. I think the role of ipilimumab in colorectal cancer would need to be explored further and is not yet ready for prime time in clinic.

Transcript Edited for Clarity 
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