Anke Reinacher-Schick was involved in the study.
Photo Credit: © Jakob Studnar
Scientific Frontline: Extended "At a Glance" Summary: Immunotherapy for Stage III Colon Cancer
The Core Concept: A highly effective clinical protocol that combines the immunotherapy atezolizumab (Tecentriq®) with standard adjuvant FOLFOX chemotherapy to treat patients with resected stage III colon cancer exhibiting deficient DNA mismatch repair (dMMR).
Key Distinction/Mechanism: Unlike conventional treatments that rely solely on cytotoxic mechanisms, this protocol integrates immunotherapy to target a biologically distinct, early-stage cancer subgroup. The addition of atezolizumab bolsters the immune system's response to dMMR tumors, resulting in a 50 percent reduction in the risk of disease recurrence or death compared to standard chemotherapy alone.
Major Frameworks/Components:
- Atezolizumab (Tecentriq®): The primary immunotherapeutic agent utilized to enhance the immune response.
- FOLFOX Chemotherapy: The established adjuvant chemotherapy regimen used as the baseline therapeutic foundation.
- Deficient DNA Mismatch Repair (dMMR): The specific genetic and biological biomarker identifying the patient subgroup eligible for this combined therapy.
- Phase III Alliance ATOMIC A021502 Trial: The global, multi-institutional clinical trial that verified the efficacy of the treatment protocol.
Branch of Science: Oncology, Immunology, Precision Medicine.
Future Application: Widespread clinical adoption as the new standard of care for early-stage dMMR colon cancer, alongside incorporation into international clinical protocols like the National Comprehensive Cancer Network (NCCN) guidelines for high-risk patient populations.
Why It Matters: This approach represents a transformative advancement in precision oncology, demonstrating the first clear and clinically meaningful benefit of immunotherapy in early-stage dMMR colon cancer. By substantially improving three-year disease-free survival rates (86.3 percent versus 76.2 percent), the protocol fundamentally upgrades the standard of care for this high-risk patient demographic.
Results from the pivotal Phase III Alliance ATOMIC A021502 trial, now published in The New England Journal of Medicine, demonstrate that adding the immunotherapy atezolizumab (Tecentriq®) to standard adjuvant chemotherapy significantly improves outcomes for patients with resected stage III colon cancer with deficient DNA mismatch repair (dMMR). The study showed a 50 percent reduction in the risk of disease recurrence or death compared with chemotherapy alone, establishing a new standard of care for this biologically distinct subgroup.
At three years, 86.3 percent of patients treated with atezolizumab in combination with FOLFOX chemotherapy remained disease-free, compared with 76.2 percent of patients receiving chemotherapy alone (hazard ratio for recurrence or death, 0.50; 95 percent confidence interval, 0.35–0.73). After a median follow-up of 40.9 months, 127 disease-free survival events were observed.
Between September 2017 and January 2023, the ATOMIC trial enrolled 712 patients following curative resection of stage III dMMR colon cancer. Participants were randomized to receive six months of standard FOLFOX chemotherapy alone or FOLFOX combined with atezolizumab, followed by an additional six months of atezolizumab monotherapy.
The findings were first presented as Late-Breaking Abstract #1 during the Plenary Session of the 2025 Annual Meeting of the American Society of Clinical Oncology (ASCO) and have now been peer-reviewed and published in The New England Journal of Medicine.
German participation in this major international academic collaboration was enabled through close cooperation between the Alliance and the AIO (Arbeitsgemeinschaft Internistische Onkologie) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG), under the national leadership of Professor Anke Reinacher-Schick (Ruhr University Bochum). AIO-affiliated study sites enrolled patients during the later recruitment phase, ensuring access for eligible patients in Germany.
“The ATOMIC trial represents a pivotal advancement in the adjuvant treatment of stage III dMMR colon cancer,” said Professor Anke Reinacher-Schick. “For the first time, immunotherapy has demonstrated a clear and clinically meaningful benefit in early-stage dMMR disease, establishing a new therapeutic standard. In Germany, rapid identification of eligible patients was facilitated by AIO’s COLOPREDICT registry, which played a key role in screening and timely enrollment.”
“This study demonstrates how international academic collaboration can translate biomarker-driven science into practice-changing clinical results,” said Professor Dirk Arnold (Asklepios Tumorzentrum Hamburg, AK Altona; AIO/GI Oncology). “The close partnership between German and U.S. investigators highlights the strength of academic research networks in advancing precision oncology.”
“This success underscores the power of multinational, academically driven research partnerships,” added Dr. Mischo Kursar, Managing Director of AIO-Studien-gGmbH. “As German Sponsor Representative, AIO-Studien-gGmbH enabled AIO sites to participate fully in this defining global trial and showcased the strength of Germany’s clinical research infrastructure.”
The clinical relevance of ATOMIC is further reflected by the inclusion of its findings in the latest National Comprehensive Cancer Network (NCCN) guidelines, reinforcing the role of immunotherapy-based adjuvant treatment strategies in high-risk patient populations.
Additional information: The trial was led globally by Frank A. Sinicrope, MD, Professor of Oncology at the Mayo Clinic and U.S. Principal Investigator within the Alliance.
AIO (Arbeitsgemeinschaft Internistische Onkologie) is a leading cooperative academic oncology working group in Germany, focused on advancing high-quality, academically led cancer research. The AIO-Studien-gGmbH serves as its operational and legal entity for clinical trial execution and international partnerships. For more information about the ATOMIC study, visit ClinicalTrials.gov/NCT02912559.
Funding: The global study in the U.S. was sponsored by the U.S. National Cancer Institute (NCI), part of the National Institutes of Health, and led by the Alliance for Clinical Trials in Oncology with participation from other NCI-funded National Clinical Trials Network (NCTN) groups. Genentech, a member of the Roche Group, provided support for the study through a Cooperative Research and Development Agreement bewteen NCI and Genentech.
Published in journal: The New England Journal of Medicine
Title: Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer
Authors: Frank A. Sinicrope, M.D., Fang-Shu Ou, Ph.D., Dirk Arnold, M.D., Walter R. Peters, M.D., Robert J. Behrens, M.D., Christopher H. Lieu, M.D., Khalid Matin, M.D., Deirdre J. Cohen, M.D., Samara L. Potter, M.D., Andrew B. Nixon, Ph.D., Lisa A Kottschade, A.P.R.N., C.N.P., Emily Kathol, Pharm.D., Wendy L. Frankel, M.D., Ardaman Shergill, M.D., Dennis Hsu, M.D., Anke Reinacher-Schick, M.D., Paul Mehan, M.D., Philip J. Gold, M.D., Maged F. Khalil, M.D., Tyler Zemla, M.S., Clare Gatten, M.A., Eileen M. O’Reilly, M.D., and Jeffrey A. Meyerhardt, M.D
Source/Credit: Ruhr-Universität Bochum
Reference Number: ongy032726_01