Combination therapy improves progression-free survival in dMMR/MSI-H metastatic colorectal cancer

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 recently 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 COMMIT 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. 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.”

Caio Max Sao Pedro Rocha Lima, MD of Wake Forest University School of Medicine, and Principal Investigator of the COMMIT trial

“Clinical trials like COMMIT are essential to advancing treatment for patients with colorectal cancer,” added Co-Principal investigator, Michael Overman, MD 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.”

The COMMIT trial (NRG-GI004/SWOG S1610; NCT02997228) was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and led by the NCI-funded NRG Oncology in collaboration with SWOG with participation from the NCI-funded national clinical trials network (NCTN) as part of a collaboration with Genentech, a member of the Roche Group, and the NCI through a Cooperative Research and Development Agreement (CRADA). Support by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI), with additional support from Genentech, a member of the Roche Group.