Is there a Role for Immune Therapy Outside of Clinical Trials for Patients With Proficient Mismatch Repair Colorectal Cancer?

At Great Debates and Updates in Gastrointestinal Malignancies in New York, New York, Michael Overman, MD, MD Anderson Cancer Center, Houston, Texas, explores whether or not there is a role for immune therapy right now in the treatment of patients with proficient mismatch repair colorectal cancer. 

Transcript: 

I'm Michael Overman, a GI medical oncologist at MD Anderson Cancer Center, and I'm happy to be here talking to you from the 2024 New York Great Debates. We had a discussion regarding the use of immune therapy as standard of care for patients with proficient mismatch repair metastatic colorectal cancer. These again are proficient mismatch repair, we do not have any approved use of immunotherapy in that subset– all the approved immunotherapy is for deficient mismatch repair.

 In that proficient mismatch repair space I am representing the no argument, I do not believe there is a standard of care role for that and I think I'll make a few points to support that.

One obvious point is we don't have any approved agents in that space or guideline-based agents in that space, a pretty simple kind of argument to make in that regard. I do think we have seen some combinations that have shown some benefit and I think we're pretty excited about some novel immune therapy combinations that may have some activity in proficient mismatch repair but again, we don't really see activity with monotherapy at PD-1s but when we look at PD-1 plus other drugs, such as VEGF TKIs, potentially new FC-engineered CTLA-4 agents, or other bispecific-based approaches there's a number of kind of different agents that are showing some immune therapy activity and proficiently repair but I think the challenges are really kind of twofold.

One is what is the best combination, what is the right combination to use? I don’t think we know that. There's a lot of different options out there and it's not clear what the right one should be. Then number 2, what population do we provide these therapies? I think if you look at the data, it does appear that we see the most activity when we look at a non-liver metastatic setting, patients that don't have metastases in the liver. We know that liver metastases have a very immune suppressive effect that appears to kind of work systemically and so the data does suggest better activity in the non-liver met patients but again, we don't have a lot of good numbers on that in regards to is it really the patients with lung only mets, the patient with lymph node only mets, the patient with peritoneal mets. I think there's some hints of interest looking at some of these novel combinations, potentially in kind of a non-liver met space, but I think there's still a lot of unknowns at this time and that for me really makes this an approach that is really better suited for clinical trial engagement to really understand what is the best combination and exactly what kind of situation in this non-liver met setting might be the approach that we should be using it.

I will say, very exciting to see hints of activity in proficient mismatch repair from immune therapy, so at a high level a very exciting occurrence and I think looking forward to a lot potential in the future, and potential role in the future with some novel combinations but, I don't think right now we're at that state and again would encourage everyone that's interested in immunotherapy for proficient mismatch repair patients to be sending those patients to centers for clinical trials.

Source: 

Overman M. Debate: Is there a role for immune checkpoint inhibition outside of a clinical trial in microsatellite stable (MSS) patients? Yes vs no. Presented at Great Debates and Updates in Gastrointestinal Malignancies. May 17-18, 2024. New York, NY.