Combination therapy improves progression-free survival for patients with metastatic dMMR colorectal cancer

by NRG Oncology

edited by Sadie Harley, reviewed by Andrew Zinin

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Patients with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer experienced a 58% reduction in the risk of disease progression or death when treated with atezolizumab (Tecentriq) plus modified FOLFOX6 and bevacizumab (Avastin), compared with atezolizumab alone, according to results from the NRG-GI004/SWOG S1610 COMMIT trial published in the Journal of Clinical Oncology. The combination also produced higher response rates and substantially reduced primary disease progression.

Approximately 5% of patients with metastatic colorectal cancer have tumors characterized by dMMR or MSI-H, a molecular subtype that is often responsive to immunotherapy. Although immune checkpoint inhibitors have transformed the treatment of dMMR/MSI-H metastatic colorectal cancer, approximately one-third of patients experience primary resistance or early disease progression with single-agent immunotherapy.

COMMIT was designed to determine whether adding chemotherapy and bevacizumab could improve outcomes. The trial enrolled patients with previously untreated dMMR/MSI-H metastatic colorectal cancer and compared atezolizumab alone with atezolizumab combined with modified FOLFOX6 chemotherapy and bevacizumab. Patients receiving the combination experienced:

• 58% reduction in the risk of progression or death (HR 0.42)
• Median progression-free survival of 24.5 months versus 5.3 months
• Objective response rate of 86% versus 46%
• Complete responses in 36% versus 19%
• Marked reduction in primary disease progression

"These findings demonstrate that combining chemotherapy and bevacizumab with immunotherapy may provide a meaningful clinical benefit for patients with dMMR/MSI-H metastatic colorectal cancer," said Caio Max Sao Pedro Rocha Lima, MD, of Wake Forest University School of Medicine and principal investigator of the COMMIT trial.

"The study showed not only longer progression-free survival, but also a dramatic reduction in the number of patients whose disease progressed as their best response to treatment. These results may help inform future treatment strategies for this patient population."

"Clinical trials like COMMIT are essential to advancing treatment for patients with colorectal cancer," added Michael Overman, MD, co-principal investigator of The University of Texas MD Anderson Cancer Center.

"The study provides evidence supporting a combination approach in the first-line setting and underscores the importance of continued collaboration to identify therapies that offer the greatest benefit for patients."

Publication details

Caio Max Sao Pedro Rocha Lima et al, COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, Journal of Clinical Oncology (2026). DOI: 10.1200/jco-25-03052

Journal information: Journal of Clinical Oncology

Key medical concepts

atezolizumabProgression-Free SurvivalBevacizumab

Clinical categories

OncologyGastroenterology Provided by NRG Oncology Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

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