The addition of atezolizumab to standard chemotherapy has achieved a remarkable 50% reduction in the risk of recurrence or death for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer, according to results from the phase 3 ATOMIC trial presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
The multicenter, randomized, open-label study enrolled 712 patients across more than 300 sites in the National Clinical Trials Network from September 2017 to January 2023. The trial sought to determine whether adding an immune checkpoint inhibitor to standard care would improve outcomes after surgical resection in this population.
Trial Design and Patient Population
Patients were eligible if they had resected stage III colon cancer with dMMR determined by immunohistochemistry, no prior chemotherapy or radiation, and an ECOG performance status of 2 or less. The median age was 64 years, and over half of patients (55.1%) were female.
After undergoing surgery, patients were randomly assigned to receive either atezolizumab plus the standard mFOLFOX6 chemotherapy regimen (oxaliplatin, leucovorin calcium, and fluorouracil) followed by 6 months of atezolizumab, or mFOLFOX6 alone in the control arm. The primary endpoint was disease-free survival (DFS), with secondary endpoints including overall survival and adverse event profile.
Significant Clinical Outcomes
At the data cutoff of February 4, 2025, with a median follow-up of 37.2 months, the combination treatment demonstrated substantial clinical benefit. At 3 years, the combination resulted in a DFS rate of 86.4% versus 76.6% for chemotherapy alone (HR, 0.50; 95% CI, 0.34-0.72; P < .0001).
"This is a substantial benefit achieved," said lead author Frank A. Sinicrope, MD, coleader of the Gastrointestinal Cancer Program and clinical investigator at Mayo Foundation in Rochester, Minnesota. Referring to the DFS curves, Sinicrope noted that "the [DFS] curve is plateauing, indicating that we're not seeing any more recurrences or death with the immunotherapy and chemotherapy combination."
Consistent Benefits Across Patient Subgroups
Subgroup analysis demonstrated positive DFS benefits across all patient populations defined by age, sex, race, tumor location, and risk group. Notably, both proximal (HR, 0.56; 95% CI, 0.38-0.83) and distal (HR, 0.31; 95% CI, 0.11-0.87) tumor locations showed favorable outcomes. T-stage analysis revealed benefits for both Tx/T1-3 (HR, 0.51; 95% CI, 0.31-0.85) and T4 (HR, 0.46; 95% CI, 0.27-0.79) classifications, while risk group analysis showed improvements in both low-risk (HR, 0.47; 95% CI, 0.24-0.94) and high-risk (HR, 0.51; 95% CI, 0.33-0.78) patients.
"No matter the patient's age, their sex, their race, their location, T-stage, or N-stage, patients are doing better with the addition of immunotherapy to chemotherapy," Sinicrope emphasized.
Safety Profile and Clinical Implementation
The safety profile of mFOLFOX6 plus atezolizumab aligned with the known safety profiles of each component, with a manageable increase in nonfebrile neutropenia being the primary additional concern.
"The most important thing about this study is that it involves a real-world population that I will see in my clinic," commented Joel Saltzman, MD, medical oncologist at Taussig Cancer Center, Cleveland Clinic. "We have seen patients in whom we thought immunotherapy would be helpful, but we weren't sure if we could integrate it into their care."
Clinical Significance and Future Impact
Patients with dMMR colon cancer carry tumors with microsatellite instability, a molecular characteristic that serves as a biomarker for predicting response to immune checkpoint inhibitors like atezolizumab, an anti-PD-L1 monoclonal antibody. While previous trials had shown benefits of immune checkpoint inhibitors in metastatic dMMR colorectal cancer, this represents the first successful demonstration in the adjuvant setting.
"These data establish this combination as a new standard treatment for patients with stage III colon cancer and dMMR," Sinicrope concluded. "We regard [these findings] as a highly impactful study that will change clinical practice, and it actually represents the first immunotherapy adjuvant study in colon cancer."
Jeffrey Meyerhardt, MD, senior author and co-chair of the Alliance Gastrointestinal Committee at Dana-Farber Cancer Institute, noted the broader implications: "The results of the ATOMIC trial are extremely compelling and demonstrate a substantial benefit to patients. Not only do they provide the evidence for a new standard of care in this subgroup of patients with colon cancer, but they also illustrate the power of the National Clinical Trials Network and federal funding from the NCI to test clinical hypotheses and ultimately improve the lives of cancer patients."
The study's completion required five years of patient accrual across more than 300 sites and would not have been feasible without federal funding from the National Cancer Institute and the cooperative group network infrastructure.
