Clinic Conversation of the Week: How to Talk With Patients About the CheckMate 8HW Trial in MSI-High/dMMR Metastatic Colorectal Cancer

This Clinic Conversation of the Week by Christopher Lieu, MD, Associate Professor and Associate Director of Clinical Research at the University of Colorado Cancer Center, explores the CheckMate 8HW study, recently presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. This trial investigated the role of immunotherapy in patients with metastatic colorectal cancer that is microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR). In this edition, Dr. Lieu explains how to talk with patients in the clinic about the study’s findings, including the efficacy of a dual immunotherapy approach with nivolumab and ipilimumab, its impact on progression-free survival, and its potential to become the new standard of care for this patient population.

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Christopher Lieu, MD: Welcome to this Clinic Conversation of the Week, a series where we explore how to discuss the latest groundbreaking research with our patients in the clinic. My name is Chris Lieu, and I’m a Gastrointestinal (GI) Medical Oncologist at the University of Colorado Cancer Center. Today, I’d like to discuss the CheckMate 8HW study as if we were having this conversation with a patient in clinic.

Here’s What I Would Say

“So, CheckMate 8HW is a study of the use of immunotherapy for patients with metastatic colorectal cancer, in a very specific patient population. That is a patient population that is microsatellite instability (MSI)–high or deficient mismatch repair (dMMR). This is simply a biomarker that tells us that the DNA repair mechanism within the colorectal cancer is dysfunctional.

Unfortunately, this only represents about 4% of our patient population with metastatic colorectal cancer, but it’s really important that we know that this biomarker exists in the patient population that is MSI-high or dMMR, because those patients may respond better to immunotherapy than they do to standard-of-care chemotherapy. In this study, the investigators were trying to answer a question: are two immunotherapy drugs better than one immunotherapy drug? And is immunotherapy in general, whether it’s two drugs or one drug, better than standard-of-care chemotherapy, which is how we typically start treatment for any patient diagnosed with metastatic colorectal cancer?

Patients were randomized—again, they had metastatic colorectal cancer, and they had this biomarker called MSI-high or dMMR—to receive two immunotherapy drugs, nivolumab and ipilimumab; one immunotherapy drug, nivolumab, by itself; or standard-of-care chemotherapy, and physicians got to choose which chemotherapy they got. We know from the prior reports of this study that patients who received immunotherapy, particularly the doublet immunotherapy of nivolumab and ipilimumab, did better. Patients receiving immunotherapy did better than patients receiving chemotherapy.

What we didn’t know, and what this recent study update showed us was: are two drugs better than one drug when it comes to immunotherapy? In this study, we looked at the time that it took for a patient’s tumor to grow—we call this progression-free survival, how long it takes for a cancer to progress or to grow. At two years, the two-drug regimen had a 24-month rate of progression-free survival of 71%. Another way of saying that is that 71% of the patients getting the two drugs of immunotherapy didn’t have any tumor growth at two years. When we looked at the group of patients who received only one immunotherapy drug, only 56% of those patients had a 24-month progression-free survival. In other words, only 56% of the patients had the tumor not grow within 24 months.

When you look at the toxicity of both regimens, you can imagine that the patients getting two immunotherapy drugs had slightly higher rates of side effects that are sometimes related to immunotherapy, whether that’s fatigue, diarrhea, or other side effects. Regardless, the toxicity between the two groups was relatively similar.

So, what the CheckMate 8HW study really taught us is that in patients who were able to receive two immunotherapy drugs, nivolumab and ipilimumab, those patients did seem to do better than patients receiving only one drug, nivolumab alone, or standard-of-care chemotherapy. This likely represents the new standard of care for patients who are newly diagnosed with metastatic colorectal cancer and have a biomarker of MSI-high or dMMR.”

About Dr. Lieu

Christopher Lieu, MD, is an Associate Professor and the Associate Director of Clinical Research at the University of Colorado Cancer Center in Aurora, Colorado. In addition, he is Co-Director of Gastrointestinal (GI) Medical Oncology at the University of Colorado Cancer Center and Vice Chair of the National Cancer Institute (NCI) Colon Cancer Task Force. Dr. Lieu specializes in the treatment of GI cancers, including colorectal, hepatocellular, esophageal, pancreatic, gastric, bile duct, anal, and gallbladder cancers. His research focuses on developmental therapeutics and resistance mechanisms to targeted therapy in GI cancers.