Targeted therapy plus immunotherapy improved outcomes in advanced metastatic colorectal cancer

MD Anderson Research News January 06, 2026

• Phase III COMMIT trial evaluated better first-line options for patients with dMMR/MSI-H metastatic colorectal cancer
• The study compared the immunotherapy atezolizumab alone versus mFOLFOX6/bevacizumab plus atezolizumab as first-line treatment 
• Median progression-free survival was 30 months for patients treated with combination therapy compared to 4.3 months for those receiving immunotherapy alone
• Combination therapy reduced the risk of disease progression or death by more than half

A new trial co-led by researchers at The University of Texas MD Anderson Cancer Center has demonstrated that combining the immunotherapy atezolizumab with standard chemotherapy (mFOLFOX6) plus the targeted therapy bevacizumab significantly improved outcomes for patients with advanced colorectal cancer compared to immunotherapy alone. 

Findings from the Phase III COMMIT trial (Abstract 14) will be presented Jan. 10 at the annual American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium. The study was co-led by senior author Michael Overman, M.D., professor of Gastrointestinal Medical Oncology.

The combination therapy achieved an overall response rate of 80.6%, compared with 46% in the immunotherapy-alone cohort. These results represent a promising advance in identifying new therapies for first-line care for metastatic colorectal cancer. 

What is the COMMIT trial and what were the outcomes of the study? 

COMMIT is a randomized Phase III clinical trial designed to evaluate whether combining atezolizumab, which blocks the PD-L1 checkpoint protein, with mFOLFOX6 and bevacizumab can improve outcomes for patients with previously untreated deficient mismatch repair (dMMR) metastatic colorectal cancer compared to immunotherapy alone.

A total of 102 participants were randomized to one of three treatment arms:

• Atezolizumab alone
• Atezolizumab with mFOLFOX6 plus bevacizumab
• mFOLFOX6 plus bevacizumab

The mFOLFOX6 plus bevacizumab arm was discontinued early, and the primary endpoint for the study was progression-free survival (PFS) between atezolizumab alone and atezolizumab with mFOLFOX6 plus bevacizumab. 

The atezolizumab combination regimen significantly reduced the risk of disease progression or deaths over atezolizumab alone. Median PFS was 30 months with the combination versus 4.3 months with atezolizumab alone. At 12 months, disease control rates were 62.9% and 32.4%, respectively. 

“These trial results suggest this treatment strategy could be an important advance in first-line care for dMMR metastatic colorectal cancer,” Overman said. “It reinforces the value of exploring combination approaches to unlock deeper and more durable responses.”

What do these findings mean for patients with dMMR colorectal cancer?

 Deficient mismatch repair (dMMR) tumors behave differently from most colorectal cancers. These tumors have trouble repairing DNA damage, which leads to many mutations. Therefore, the tumors tend to be more visible to the immune system and often are more responsive to immunotherapy. 

Understanding whether immunotherapy works best alone or when combined with chemotherapy and bevacizumab is critical. The results from all three trial arms will help doctors determine which approach delivers the longest disease control with the fewest side effects for patients with dMMR metastatic colorectal cancer. 

Researchers will continue to follow patients and report additional outcomes, including overall survival and quality of life.

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This work was supported by Genentech, Inc. and the National Institutes of Health (U10 CA180868, CA180822, CA180888, UG1 CA189867, U24 CA196067). A complete list of collaborating authors and their disclosures can be found with the abstract.