The Food and Drug Administration has approved atezolizumab, an immunotherapy drug, in combination with chemotherapy for certain patients with stage 3 colon cancer after surgery. The treatment targets tumors with deficient DNA mismatch repair, known as dMMR, which affects about 15% of colon cancers.
ATOMIC Trial Results
The approval stems from the phase 3 ATOMIC clinical trial led by Mayo Clinic. The study enrolled 712 patients with stage 3 dMMR colon cancer who had undergone surgical removal of their tumors. Participants were randomly assigned to receive either standard chemotherapy alone or chemotherapy combined with atezolizumab, followed by additional doses of the immunotherapy drug.
At the three-year mark, 86.3% of patients receiving immunotherapy plus chemotherapy remained alive and free of disease, compared to 76.2% of those on chemotherapy alone. The findings, published in The New England Journal of Medicine, showed a 50% reduction in the risk of cancer recurrence or death.
Moving Treatment Earlier
Dr. Frank Sinicrope, a Mayo Clinic oncologist and leader of the ATOMIC study, noted that this is the first study demonstrating the benefit of immunotherapy after surgical resection in locally advanced colon cancer with dMMR. “Instead of waiting until a patient’s colon cancer has returned or spread, we can now use immunotherapy earlier when patients have undergone surgery and are able to prevent or markedly reduce the chance of recurrence,” he said.
Immune checkpoint inhibitors like atezolizumab have previously been used primarily for advanced or metastatic dMMR colorectal cancer. The ATOMIC trial explored whether activating the immune system post-surgery could eliminate remaining microscopic cancer cells and increase cure rates. Tumors with dMMR accumulate multiple mutations, making them more recognizable to the immune system.
Impact on Younger Patients
The approval arrives as colorectal cancer rates among younger adults continue to rise. More than one-quarter of patients enrolled in the ATOMIC trial were under 50 years old. The study also included individuals with Lynch syndrome, the most common inherited cause of colorectal cancer, which frequently leads to dMMR tumors and earlier onset.
“For patients who develop colon cancer at a young age, preventing recurrence can translate into decades of life gained,” Dr. Sinicrope emphasized. “Being able to offer an effective treatment such as immunotherapy to improve the survival of these patients is especially meaningful for them and their families.”
Research Foundation
The ATOMIC trial built upon years of research into dMMR colon cancer biology. Dr. Sinicrope and colleagues had previously observed that these tumors contain large numbers of inflammatory and immune cells, including those targeted by immune checkpoint inhibitors. This provided the scientific rationale for testing immunotherapy as an adjunct to chemotherapy in the curative setting.
The study was conducted through the Alliance for Clinical Trials in Oncology, part of the National Cancer Institute-supported National Clinical Trials Network, with patient participation from the U.S. and Germany. The National Full Cancer Network had already updated its treatment guidelines to include the atezolizumab plus chemotherapy regimen based on ATOMIC findings prior to FDA approval.
“The patients who participated in ATOMIC made this advance possible, and their contribution will change how we treat patients with dMMR colon cancer here and around the world,” Dr. Sinicrope stated.
The National Cancer Institute of the National Institutes of Health and Genentech provided funding for the ATOMIC study. A complete list of authors, disclosures, and funding details is available in the New England Journal of Medicine publication.