The combination regimen of FOLFOX chemotherapy (leucovorin, fluorouracil, and oxaliplatin), bevacizumab, and atezolizumab led to a statistically significant improvement in progression-free survival compared with atezolizumab monotherapy for the first-line treatment of patients with deficient mismatch repair or microsatellite instability–high (dMMR/MSI-H) metastatic colorectal cancer, according to findings from the COMMIT study presented in a press briefing ahead of the 2026 ASCO Gastrointestinal Cancers Symposium (Abstract 14).
“The combination arm was superior to the single arm in progression-free survival with a hazard ratio of 0.43, suggesting a 57% improvement in progression-free survival favoring the combination arm. In addition to the median progression-free survival, there was improvement in radiologic response, both complete and partial responses,” said lead study author Caio Max Sao Pedro Rocha Lima, MD, MS, Medical Oncologist and Hematologist at Atrium Health Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, during the press briefing.
Background
Based on the results of the KEYNOTE-177 trial, single-agent pembrolizumab has become a first-line standard of care for patients with dMMR/MSI-H metastatic colorectal cancer; however, patients typically experienced disease progression within 12 months. The combination of FOLFOX and atezolizumab showed a disease-free survival benefit over FOLFOX alone in the adjuvant setting for patients with stage III dMMR/MSI-H colon cancer in the ATOMIC trial.
A prior phase Ib trial explored the triplet combination of FOLFOX, bevacizumab, and atezolizumab in 30 patients with proficient mismatch repair/microsatellite-stable metastatic colorectal cancer who were naive to oxaliplatin and showed antitumor activity and no safety signals.
Study Methods
The COMMIT trial was originally designed to explore the use of FOLFOX and bevacizumab with or without atezolizumab compared with atezolizumab monotherapy in patients with dMMR/MSI-H metastatic colorectal cancer who had not received prior systemic therapy for metastatic disease. However, due to the results of the KEYNOTE-177 trial, the trial design was amended on June 4, 2020, to discontinue the FOLFOX and bevacizumab doublet arm. The study was also reduced to 120 planned participants between the two arms with 80% power needed to detect a hazard ratio (HR) of 0.6 for progression-free survival.
Key Findings
The study's preplanned interim analysis was conducted at a median follow-up of 3.5 years after 45 progression-free survival events had occurred, at which point the primary endpoint was met and the Data Safety Monitoring Committee recommended closing the study early.
The HR for progression-free survival for the triplet regimen vs atezolizumab monotherapy was 0.439 (95% confidence interval [CI] = 0.23–0.84; P = .0103). At 12 months, the progression-free survival rate was 66.7% in the triplet arm vs 35.1% in the atezolizumab monotherapy arm; at 24 months, the progression-free survival rates were 53.7% and 31.6%, respectively.
The overall response rate was 86.1% with FOLFOX, bevacizumab, and atezolizumab compared with 46% with single-agent atezolizumab. Complete responses were seen in 36.1% of patients in the triplet arm and in 18.9% of patients in the monotherapy arm; partial responses were seen in 50% and 27%, respectively. Only 2.8% of patients experienced disease progression in the triplet arm vs 32.4% in the monotherapy arm. The disease control rate at 1 year was 62.9% with the combination regimen and 32.4% with the immunotherapy alone.
No difference was observed between the two arms in terms of overall survival (HR = 1.04; 95% CI = 0.47–2.28; P = .90).
Adverse events were significantly more common in the triplet regimen arm with rates of any-grade adverse events of 92.7% and 73.2% for grade 3/4 adverse events compared with 80.5% and 41.5%, respectively, in the monotherapy arm. The most common adverse events were infection, neutropenia, hypertension, diarrhea, fatigue, and sensory neuropathy. Rates of grade 3/4 neutropenia and infection were significantly higher in the triplet arm than in the atezolizumab alone arm. Hypoalbuminemia was only seen in the atezolizumab monotherapy arm. Four patients died during treatment in the triplet regimen arm vs one in the atezolizumab arm.
Dr. Rocha Lima added that further research will focus on identifying which patients require intensification of treatment beyond single-agent immunotherapy.
ASCO Expert Vishwanath Sathyanarayanan, MD, Lead Oncosciences, Karnataka Region, Senior Consultant and Academic Advisor, Apollo Hospitals, Bangalore, India, commented during the press briefing: “The median time to progression with this combination has been much better as compared to atezolizumab, and this definitely holds promise as a potential new treatment option for these patients.”
Disclosure: The study was funded by the National Cancer Institute and Genentech. For full disclosures of the study authors, visit coi.asco.org.
