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Overman Highlights Latest Nivolumab Results in MSI-H/dMMR mCRC

Angelica Welch
Published: Thursday, Feb 08, 2018

Michael J. Overman, MD
Michael J. Overman, MD
Updated findings from the CheckMate-142 study presented at the 2018 Gastrointestinal Cancers Symposium continued to support the use of nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) for previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC).

An update of patients receiving nivolumab monotherapy in CheckMate-142 presented by Michael J. Overman, MD, showed that nivolumab continued to provide clinically meaningful and durable responses in the 74 patients treated, with a deepening of responses with longer follow-up.1 At 21 months’ follow-up, the overall response rate (ORR) was 34%, including a complete response (CR) rate of 9% (n = 7), and a partial response rate of 24% (n = 18). The median overall survival (OS) was not yet reached.

A separate abstract presented at the symposium reported data for the nivolumab/ipilimumab cohort of CheckMate-142.2 The findings showed a durable clinical benefit for the combination over a median follow-up of 13 months, with an ORR of 55% and a median duration of response that was not reached.

Based on previously reported results for the 74-patient nivolumab monotherapy group from CheckMate-142, the FDA approved single-agent nivolumab in August 2017 for the treatment of adult and pediatric patients with MSI-H/dMMR mCRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

In an interview with OncLive at the symposium, Overman, associate professor in the Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, discussed both the updated findings he presented at the meeting for the single-agent CheckMate-142 cohort, as well as the latest combination data from the pivotal trial.

OncLive: Can you please provide some background information on this study?

Overman: This an updated analysis of the CheckMate-142 study. The main arm in that was single-agent nivolumab in a 2-stage design, where we evaluated the idea of using anti–PD-1 therapy in this population, which is dMMR/MSI-H mCRC. Therefore, dMMR patients have a deficiency in DNA repair, which leads to a lot of mutations. There was a hypothesis that this group would be responsive to immune-based therapy, and that is how this study initiated. 

We have previously presented and published our results in Lancet Oncology, so this is a further update. The prior data was of a 13-month median follow-up, and this is a 21-month median follow-up for that 74-patient nivolumab monotherapy arm. 

What are the updated findings?

Basically, what we are showing is that, as previously expected, this therapy works in a very high percentage of patients, and we see that continuing. We do see some interesting issues in regard to depth of response; we previously reported a 3% complete CR rate, and this is now up to a 9% CR rate. 

The thing that is the most exciting and interesting is that previously, on our PFS and OS curves, there was some flattening of the curve on the tail end, so now we have further follow-up and we see that the curve stays completely flat. If you look at the PFS curve at 12 months, our PFS is 44% and at 18 months it remains at 44%. Survival is very similar; survival is 72% at 12 months and then 67% at 18 months. There is this kind of stabilization—when this therapy works in those patients, it appears to be durable and long lasting. That is the exciting point of this data; our update supports the idea that this is a durable therapy and it enters that idea of possibly curing patients with mCRC. The data seem to suggest that is the probably the case, although it is a little bit early to make that strong of a statement.

How do you think these findings will affect the treatment landscape of mCRC?

It has had a pretty big impact, but the issue is that this therapy is a very active therapy. That is what the previous data have said, and that is what is [also found] in this update. This means identifying these patients is really critical. We have a therapy now that works extremely well and potentially cures a fraction of patients. It has really moved into this idea of universal testing in CRC; this means that all patients with CRC should have MSI testing. That is the push that has been put out, as well as that testing can be by immunohistochemical staining, pathologic complete response, or next-generation sequencing. It doesn't matter how to find these patients, it is just that we should be identifying them. Identifying that group is a critical take-home message.

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