The Alliance for Clinical Trials in Oncology (Alliance) today announced that the U.S. Food and Drug Administration has approved the immunotherapy drug atezolizumab (Tecentriq®) in combination with fluoropyrimidine and oxaliplatin chemotherapy, for the adjuvant treatment of patients with stage III colon cancer with deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR). The approval is based on findings from 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). The study demonstrated that patients with stage III colon cancer whose tumors had mismatch repair deficiency (dMMR) experienced significantly improved disease-free survival, a surrogate for overall survival, when atezolizumab was added to standard adjuvant chemotherapy following surgery.
"The FDA approval of atezolizumab for patients with stage III dMMR colon cancer is a significant milestone for patients and for the Alliance. The ATOMIC trial demonstrates the potential of introducing immunotherapy earlier in the course of cancer treatment, when the disease is still potentially curable, with the goal of preventing recurrence and increasing the number of patients who can be cured. It also demonstrates the power of the National Cancer Institute's National Clinical Trials Network to conduct large, definitive trials that answer important questions in cancer management and translate those findings into new standard of care," said Evanthia Galanis, MD, DSc, Group Chair of the Alliance for Clinical Trials in Oncology. "The ATOMIC results show what is possible when investigators across the country come together around a common goal. We are proud that research led through the Alliance has contributed to an FDA-approved treatment option that improves outcomes for patients with colon cancer.
From September 2017 through January 2023, the ATOMIC trial enrolled 712 participants across the United States and in Germany to evaluate adjuvant treatment strategies for patients with stage III colon cancer with dMMR. The study examined whether adding atezolizumab to standard adjuvant chemotherapy could improve outcomes in this biologically distinct population. Findings recently published in The New England Journal of Medicine showed that this approach reduced the risk of cancer recurrence or death by 50%. After three years, 86.3% of patients remained disease-free, compared with 76.2% of those receiving chemotherapy alone. These results represent the first demonstrated benefit of adjuvant immunotherapy in early-stage dMMR colon cancer.
The results of ATOMIC provide compelling evidence that immunotherapy can play an important role in reducing the risk of recurrence and death after surgery for patients with stage III dMMR colon cancer. The FDA approval of atezolizumab based on these findings is an important step in bringing the benefits demonstrated in the trial into routine clinical practice. This approval also reinforces the importance of understanding the molecular characteristics of a patient's tumor and using that information to guide treatment. We are grateful to the patients and investigators who made this study possible, and helped establish a new treatment regimen for patients with this disease."
Frank A. Sinicrope, MD, Alliance Study Chair, Professor of Oncology and Clinical Investigator of the Mayo Foundation, Mayo Clinic Comprehensive Cancer Center
The trial was designed with disease-free survival as the primary endpoint, while overall survival and safety were designated as secondary endpoints. This design enabled a comprehensive assessment of both the efficacy and safety of integrating immunotherapy into the adjuvant treatment of stage III dMMR colon cancer.
Colorectal cancer remains the second leading cause of cancer-related death worldwide. For all patients with stage III colon cancer, the standard adjuvant treatment has long been chemotherapy with a fluoropyrimidine and oxaliplatin, such as the FOLFOX regimen. However, dMMR tumors are less sensitive to fluoropyrimidine-based chemotherapy, and a substantial risk of recurrence remains despite treatment. This unmet need provides a strong rationale for biomarker-driven approaches such as the addition of immunotherapy evaluated in ATOMIC.
Alliance ATOMIC (A021502) trial was sponsored by the National Cancer Institute (NCI), part of National Institutes of Health, led by Alliance and conducted in the NCI funded National Clinical Trials Network (NCTN). Genentech, a member of the Roche Group, provided support to the study through a Cooperative Research and Development Agreement with the NCI.
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