The results of an international phase 3 clinical trial sponsored by the National Cancer Institute show that patients with deficient mismatch repair (dMMR) colon cancer that are treated with the chemoimmunotherapy combination of FOLFOX and atezolizumab had a 50% reduction in disease recurrence and death compared to those treated with chemotherapy alone.

The research was presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

The ATOMIC randomised study tested whether adding the immunotherapy drug atezolizumab to FOLFOX chemotherapy improved outcomes for patients with stage III dMMR colon cancer, as compared to FOLFOX chemotherapy alone. The study enrolled 712 patients. The median age was 64 years old and about half (55.1%) were female.

There were 355 patients randomly assigned to receive atezolizumab plus FOLFOX and 357 patients randomly assigned to receive FOLFOX alone.

Key Findings

After a median follow-up of 37.2 months:

• Out of 712 patients, 124 patients in the trial had a disease-free survival (DFS) event of cancer recurrence or death.
• In the atezolizumab plus FOLFOX group, 86.4% of patients did not have any evidence of cancer after 3 years. In the FOLOFX alone group, 76.6% of patients had not experienced any evidence of cancer recurrence or death.
• Patients treated with atezolizumab plus FOLFOX had a 50% lower risk of recurrence and death compared to patients treated with FOLFOX alone. The atezolizumab plus FOLFOX treatment was effective across all subgroups, including patients older than age 70, low-risk patients and high-risk patients.

Severe side effects (grade 3 and higher) were experienced in both treatment groups but were manageable and consistent with the known toxicities of the drugs.

“Colon cancers with deficient mismatch repair have shown relative resistance to chemotherapy. However, these tumours show a high burden of mutations which are immunogenic and can lead to stronger anti-tumour immune responses when treated with immunotherapy. These findings apply to patients with Lynch syndrome, the most common hereditary colon cancer syndrome, and the more common deficient mismatch repair colon cancers that are sporadic in that they can’t be traced to a known hereditary cause or family history,” said lead study author Frank A. Sinicrope, MD, Mayo Clinic, Rochester, Minnesota.

“This study will change the standard of care for the subset of patients with deficient DNA mismatch repair colon cancer by incorporating atezolizumab to standard of care FOLFOX chemotherapy in the adjuvant setting. A study like this could never be completed without the multicenter structure of a cooperative group trial that has National Cancer Institute funding given the small percentage of patients with this distinct form of colon cancer,” said Joel Saltzman, MD, Vice Chair of Regional Oncology at Taussig Cancer Center, Cleveland Clinic, and an expert in gastrointestinal cancers.

The ATOMIC clinical trial is ongoing, and the study investigators will continue to follow these patients. They will also study biospecimens from the trial and try to identify biomarkers that can predict which patients treated with chemoimmunotherapy are more likely to receive benefit as well as who might be at a higher risk of cancer recurrence.

Source: ASCO