March 25, 2026 — A new study from researchers at the Alliance for Clinical Trials in Oncology (Alliance) shows that patients with stage III colon cancer with deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR) had significantly better outcomes when the immunotherapy drug atezolizumab (Tecentriq®) was added to standard chemotherapy after surgery. The phase III Alliance ATOMIC A021502 trial, sponsored by the National Cancer Institute (NCI) and conducted in partnership with Genentech, a member of the Roche Group, and the German group Arbeitsgemeinschaft Internistische Onkologie (AIO), found that this approach lowered the risk of the cancer returning or causing death by 50%, with 86.3% of patients remaining disease-free at three years compared with 76.2% receiving chemotherapy alone. The findings, now published in The New England Journal of Medicine, provide strong evidence that adding immunotherapy to chemotherapy can improve clinical outcome for this group of patients and establishes a new therapeutic standard for this biologically distinct subset of colon cancer.
"The results of this study represent a pivotal advancement for the treatment of non-metastatic dMMR colon cancer," said Alliance Study Chair Frank A. Sinicrope, MD, Professor of Oncology and Clinical Investigator of the Mayo Foundation at the Mayo Clinic Comprehensive Cancer Center. "The demonstrated improvement in outcomes supports a fundamental shift in how we approach adjuvant therapy for this molecular subgroup. These results provide compelling evidence that will inform and elevate the standard of care."
The ATOMIC trial—an international phase III study that evaluated adjuvant treatment strategies for stage III colon cancer with deficient DNA mismatch repair (dMMR) or microsatellite instability—examined whether adding atezolizumab to standard chemotherapy could improve outcomes in this biologically distinct population. Conducted across the United States and Germany from September 2017 through January 2023, the trial enrolled 712 patients following cancer resection, including one pediatric participant. All patients were included in the second interim analysis reviewed by the Alliance Data and Safety Monitoring Board (DSMB) in February 2025. Results from this analysis were presented in a late-breaking abstract at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Participants had a median age of 64 years, and women comprised slightly more than half of the cohort (55.1%). Patients were equally randomized to receive either six months of standard adjuvant FOLFOX or the same chemotherapy paired with atezolizumab (anti-PD-L1), followed by an additional six months of atezolizumab monotherapy. Randomization was stratified by T and N stage as well as tumor location, with the majority (83.7%) having proximal tumors; 46.1% were categorized as clinical low risk (T1-3N1) and 53.9% as high risk (T4 and/or N2).
The trial was designed with disease-free survival (DFS) as the primary endpoint, while overall survival (OS) and the adverse event (AE) profile were designated secondary endpoints. This structure enabled a comprehensive assessment of both the efficacy and safety of integrating immunotherapy into the adjuvant setting for dMMR stage III colon cancer.
Results from the ATOMIC trial demonstrate that the addition of atezolizumab resulted in a statistically significant improvement in patient DFS. The 36-month disease-free survival was 86.3% (95% confidence interval [CI], 81.8 to 89.8) in the atezolizumab group, as compared with 76.2% (95% CI, 70.9 to 80.6) in the FOLFOX alone group (hazard ratio for recurrence or death, 0.50; 95% CI, 0.35 to 0.73). The median follow-up was 40.9 months; 127 DFS events were observed.
The combination regimen was generally well tolerated, with a safety profile consistent with known toxicities of FOLFOX and atezolizumab. Immune-related adverse events (irAEs) were manageable and occurred in line with expectations based on previous atezolizumab studies. No new safety signals were identified.
"From a statistical standpoint, the results of Alliance A021502 are compelling," said Fang-Shu Ou, PhD, Associate Professor of Biostatistics at Mayo Clinic, and lead biostatistician on ATOMIC. "The data indicate a clear, statistically significant improvement in patient outcomes, with minimal variability. The strength of the evidence is robust, and the findings strongly support the potential for this treatment to make a meaningful difference in clinical practice."
Colorectal cancer is a leading cause of cancer-related death worldwide. For patients with stage III colon cancer, the standard adjuvant treatment remains a combination of chemotherapy drugs such as 5-FU or capecitabine and oxaliplatin (FOLFOX regimen), established in the 1990s through trials that showed improved DFS. However, patient outcomes remain suboptimal, highlighting the need for more effective, biomarker-driven therapies as shown for dMMR tumors in ATOMIC.
"Despite millions of new colorectal cancer diagnoses each year, many patients—especially those with advanced disease—still have limited treatment choices," 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. "The ATOMIC trial suggests a new direction: combining chemotherapy with immunotherapy to enlist the body's own immune system in the fight against cancer. This approach could offer patients a significantly more powerful path forward."
The latest National Comprehensive Cancer Network (NCCN) guidelines now include the results of the ATOMIC trial and apply them to patients with stage II T4bN0 colon cancer (tumors that have grown outward locally but have not spread to lymph nodes or elsewhere) as well.
"Our findings highlight why every patient diagnosed with colon cancer should have MMR testing," Dr. Sinicrope concluded. "This testing helps identify Lynch syndrome and also shows whether a patient may benefit from immunotherapy."
ATOMIC was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and 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]
