COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer.
Publication/Presentation Date
7-29-2026
Abstract
PURPOSE: Immunotherapy for frontline mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective; however, nearly half of the patients treated with single-agent PD-1 therapy will progress within 12 months. Preclinical studies in CRC and clinical data from other cancers suggest that vascular endothelial growth factor inhibition and chemotherapy can synergize with PD-L1 inhibition.
METHODS: The NRG-GI004/SWOG-S1610 (COMMIT) three-arm prospective phase III open-label trial randomly assigned first-line dMMR/MSI-H mCRC patients (1:1:1) to either: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m², and 46-hour infusional 5-FU 2,400 mg/m²)/bevacizumab (FFX/bev), or atezolizumab (atezo) monotherapy (840 mg IV once every 2 weeks), or the combination of FFX/bev/atezo. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Because of KEYNOTE 177 results, the FFX/bev arm was closed after 20 patients were enrolled. The study continued with atezo alone versus FFX/bev/atezo, with a revised sample size of 100 patients in the two remaining arms (120 patients across all three arms).
RESULTS: From November 2017 to March 2025, a total of 102 patients were enrolled in the three arms: FFX/bev: n = 20, atezo: n = 41, and FFX/bev/atezo: n = 41. At a median follow-up of 46 months for the two arms (median age: 63.3 years; 47.6% female; 23.2%
CONCLUSION: The combination of FFX/bev plus atezo led to significantly longer PFS compared with atezo monotherapy in the first-line treatment of dMMR/MSI-H mCRC.
First Page
2503052
Last Page
2503052
ISSN
1527-7755
Published In/Presented At
Rocha Lima, C. M. S. P., Yothers, G., George, T. J., Hochster, H. S., Sanoff, H. K., Cohen, D. J., Guthrie, K. A., Jacobs, S. A., Saeed, A., Kopetz, S., Colangelo, L. H., Freeman, T. J., Cole, S. W., Khalil, M., Devanna, S., Zuckerman, D. S., Hong, T. S., Henry, N. L., Ganz, P. A., Blanke, C. D., … Overman, M. J. (2026). 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 : official journal of the American Society of Clinical Oncology, JCO2503052. Advance online publication. https://doi.org/10.1200/JCO-25-03052
Disciplines
Medicine and Health Sciences
PubMedID
42525921
Department(s)
Department of Medicine, Hematology-Medical Oncology Division
Document Type
Article