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First-Line IO Combo Promising in mCRC

— Heinz-Josef Lenz, MD, discusses updated efficacy data in Checkmate 142

MedpageToday

The was presented at the , exploring an immunotherapy treatment combination in patients with metastatic colorectal cancer whose tumors were microsatellite instability (MSI)-high or mismatch repair deficient.

In this exclusive ڴŮ video, the study's lead author, , co-leader of the Gastrointestinal Cancers Program at the USC Norris Comprehensive Cancer Center in Los Angeles, discusses the findings.

Following is a transcript of his remarks:

It's my pleasure to update you on . As you know, this was a multi-cohort study, phase II study, and the cohort I'm reporting is the MSI-high metastatic colon cancer patient cohort treated in first line with nivolumab and ipilimumab. The data we presented originally at ESMO [the European Society for Medical Oncology] last year had a median follow-up of 15 months. [At] ASCO we presented a median follow-up of 24 months.

And what is exciting is that the response rate, the efficacy of this combination, has improved and increased. The partial response rate is now 69%. And what is extremely exciting is that 13% are complete responders. So with longer time, we see increasing efficacy of the first-line immunotherapy combination of a PD-1 and a CTLA-4 inhibitor in this patient population.

The duration of response, the duration of progression-free survival, and the duration of overall survival have not been reached. The 2-year PFS [progression-free survival] rate is still 74%. And the 2-year overall survival rate is 79%, indicating incredible lasting response rates and control of disease in this patient population, which is known not to do very well with chemo or targeted agents -- indicating, and further supporting of, a very robust and durable effect of this immunotherapy in this particular molecular-defined patient population.

There are no new safety signals. It has been extremely well-tolerated -- only 7% of patients discontinued because of side effects. So we are very excited about it. And I'm sure you also heard the clinical trial outcome data on KEYNOTE-177, which also showed that pembrolizumab is significantly superior to chemotherapy in this patient population.

What is interesting and is maybe the difference as I fully understand [the results] -- CheckMate 142 is a much smaller study with 45 patients -- is we don't see the 30% progression of disease. So there are a lot of questions raised such as how important are CTLA-4 inhibitors?

Will that change the potential efficacy in first line? This needs to be further explored, investigated, but certainly the MSI-high patients benefit in a significant way from immunotherapies; whether we need CTLA-4 inhibition needs to be explored in future studies. But there is certainly now interesting data showing that this combination is very effective and long lasting with no significant side effect issues.

So I think if you see a patient tomorrow in your clinic with an MSI-high metastatic colon cancer, you should consider immunotherapy. The data from KEYNOTE-177, as well as CheckMate 142, are very clearly demonstrating a higher efficacy -- and in KEYNOTE-177, a higher efficacy than chemotherapy.

We already knew MSI-high tumors do not do well with the aggressive chemotherapy or any of the targeted agents. As you know, the NCCN [National Comprehensive Cancer Network] already included nivo-ipi as a first-line treatment option in patients who may not be candidates for chemotherapy.

So this is already in our guidelines and we should act on it, particularly with further data presented at this ASCO with KEYNOTE-177 and further, longer follow-up with continued higher efficacy profiles with nivo-ipi.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.