June 1, 2025 — The Alliance for Clinical Trials in Oncology announced today results from ATOMIC (A021502), a phase III trial evaluating standard chemotherapy alone or combined with atezolizumab (Tecentriq®) in treating patients who have surgically resected stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR). The study, sponsored by the National Cancer Institute (NCI) and conducted in partnership with Genentech, a member of the Roche Group, met its primary endpoint, demonstrating a statistically significant improvement in disease-free survival (DFS) with the addition of atezolizumab, an anti-PD-L1 monoclonal antibody, to standard adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin). The data are being presented today at 1:05 pm CDT/2:05 pm ET during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (LBA1) by Alliance Study Chair Frank Sinicrope, MD.
"This is a landmark study for the treatment of patients with dMMR colon cancer," said Dr. Sinicrope, Professor of Oncology and Clinical Investigator of the Mayo Foundation at the Mayo Clinic Comprehensive Cancer Center. "For the first time, we're seeing a clinically meaningful benefit of adjuvant immunotherapy combined with chemotherapy in resected colon cancer patients significantly increases the chances of living longer with recurrence of their disease. At three years, patients who received atezolizumab had 50% less risk of disease recurrence or death."
ATOMIC is an international multicenter, randomized, and open-label phase III trial. From September 2017 to January 2023, the trial enrolled 712 patients with resected stage III dMMR colon cancer in the United States and Germany, including 1 pediatric patient. All were included in the second interim analysis reviewed in February 2025 by the Alliance Data and Safety Monitoring Board (DSMB). The median age of patients was 64 years, and more than half (55.1%) were female. Patients were randomized 1:1 into two treatment groups to receive either 6 months of standard adjuvant FOLFOX chemotherapy alone (n=357 patients) or FOLFOX combined with atezolizumab with the atezolizumab continued as monotherapy for an additional 6 months (n= 355). Patients were stratified by T and N stage in addition to primary tumor site (83.8% proximal; 46.1% clinical low risk, and 53.9% high risk). The primary endpoint was DFS; secondary endpoints were overall survival (OS) and adverse event (AE) profile.
Results from the ATOMIC trial presented today at ASCO demonstrate that the addition of atezolizumab resulted in a statistically significant improvement in DFS of patients, reducing the instantaneous risk of disease recurrence or death by 50% for patients treated with atezolizumab in combination with chemotherapy, compared to those receiving chemotherapy alone (hazard ratio for DFS, 0.50; 95% confidence interval [CI], 0.34 to 0.72). The 36-month disease-free survival was 86.4% (95% CI, 81.8 to 89.9) in the atezolizumab group, as compared with 76.6% (95% CI, 71.3 to 81.0) in the FOLFOX alone group. The median follow-up was 37.2 months; 125 DFS events were observed. "These highly statistically significant results (p<0.0001) underscore the potential of atezolizumab in combination with standard chemotherapy to be practice changing for patients with stage III colon cancer and dMMR," said Fang-Shu Ou, PhD, Associate Professor of Biostatistics at Mayo Clinic, and lead biostatistician on ATOMIC.
The safety profile of the combination regimen was consistent with known toxicities of FOLFOX and PD-L1 blockade. Immune-related adverse events (irAEs) were manageable and occurred in line with expectations based on previous atezolizumab studies.
Colorectal cancer is a leading cause of cancer-related death worldwide. Until now, the only adjuvant treatment for patients with stage III colon cancer has been with standard adjuvant chemotherapy drugs such as 5-fluorouricil (or capecitabine) and oxaliplatin (FOLFOX regimen). However, patient outcomes remain suboptimal, highlighting the need for more effective, biomarker-driven therapies as shown for dMMR tumors in ATOMIC.
"Every year, millions of people are diagnosed with colorectal cancer worldwide, many of whom face limited treatment options—especially at advanced stages. The ATOMIC trial incorporates immunotherapy that can enhance the ability of the body's immune system to attack cancer cells. The potential impact for patients is substantial," noted Eileen O'Reilly, MD, from Memorial Sloan Kettering Cancer Center and Jeffrey Meyerhardt, MD, MPH, from Dana-Farber Cancer Institute, who co-chair the Gastrointestinal Committee for the Alliance.
ATOMIC is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and was being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology 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). The trial was also open in partnership with the German group Arbeitsgemeinschaft Internistische Onkologie (AIO). To learn more about the ATOMIC trial, visit ClinicalTrials.gov .
[Support by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology); and Genentech, a member of the Roche Group]
