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Key Investigations in Advanced Colorectal Cancer

Insights from: Wells A. Messersmith, MD, FACP, University of Colorado Cancer Center
Published: Wednesday, Jun 20, 2018



Transcript: 

Wells A. Messersmith, MD, FACP: The key questions in advanced colorectal cancer have to do with novel therapeutics and biomarkers. In terms of novel therapeutics, there’s a lot of interest in immunotherapy. We know that in microsatellite-high colorectal cancer, which is a small subset, immunotherapy has benefit. The questions are, really, should we use 1 or 2 immunotherapies at a time, what are the best predictive markers in those patients, and, frankly, how long should we give them for? Is there a point where we can stop?

For the vast majority of patients, however—the microsatellite-stable patients—immunotherapy has not been effective, and so there’s a lot of interest in phase I and phase II trials to try to pick up combinations of immunotherapy that will turn microsatellite-stable colorectal cancer from a disease where immunotherapy has not been effective into a disease where it can be effective. Unfortunately, there was a press release recently regarding a combination that had some promise looking at a PD-L1 inhibitor and a MEK inhibitor. Unfortunately, that trial was not positive. I think the hunt will continue to try to find some type of immunotherapy combination that will be effective for microsatellite-stable colorectal cancer.

There’s also a lot of interest in biomarkers in terms of targeted therapies. For instance, can we use circulating tumor DNA from blood tests, which would, hopefully, represent the overall tumor burden in a patient, rather than biopsying one lesion or another, which is invasive, can have complications, and is more expensive? Can we just use a blood test to guide us in terms of what the best therapy would be? Finally, the other thing we’re seeing in 2018 is a sequencing question. Should we use drug A before drug B or drug B before drug A? What is the difference in outcome when we do those types of things?

Transcript Edited for Clarity 
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Transcript: 

Wells A. Messersmith, MD, FACP: The key questions in advanced colorectal cancer have to do with novel therapeutics and biomarkers. In terms of novel therapeutics, there’s a lot of interest in immunotherapy. We know that in microsatellite-high colorectal cancer, which is a small subset, immunotherapy has benefit. The questions are, really, should we use 1 or 2 immunotherapies at a time, what are the best predictive markers in those patients, and, frankly, how long should we give them for? Is there a point where we can stop?

For the vast majority of patients, however—the microsatellite-stable patients—immunotherapy has not been effective, and so there’s a lot of interest in phase I and phase II trials to try to pick up combinations of immunotherapy that will turn microsatellite-stable colorectal cancer from a disease where immunotherapy has not been effective into a disease where it can be effective. Unfortunately, there was a press release recently regarding a combination that had some promise looking at a PD-L1 inhibitor and a MEK inhibitor. Unfortunately, that trial was not positive. I think the hunt will continue to try to find some type of immunotherapy combination that will be effective for microsatellite-stable colorectal cancer.

There’s also a lot of interest in biomarkers in terms of targeted therapies. For instance, can we use circulating tumor DNA from blood tests, which would, hopefully, represent the overall tumor burden in a patient, rather than biopsying one lesion or another, which is invasive, can have complications, and is more expensive? Can we just use a blood test to guide us in terms of what the best therapy would be? Finally, the other thing we’re seeing in 2018 is a sequencing question. Should we use drug A before drug B or drug B before drug A? What is the difference in outcome when we do those types of things?

Transcript Edited for Clarity 
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