Understanding the ATOMIC Trial: Immunotherapy’s Impact in Stage III dMMR Colon Cancer

To better understand the role of immunotherapy in colon cancer, we spoke with Dr. Frank A. Sinicrope, a gastroenterologist and oncologist at Mayo Clinic who treats colon cancer, about the ATOMIC trial. This study examined whether adding immunotherapy to standard chemotherapy after surgery could improve outcomes for patients with stage III colon cancer whose tumors have deficient mismatch repair (dMMR), a subgroup that historically has not responded as well to chemotherapy alone.

Dr. Sinicrope explained that while these tumors are known to respond to immunotherapy in advanced disease, it was previously unclear whether that benefit would extend to earlier-stage settings. Because dMMR tumors carry a high number of mutations, they are more easily recognized by the immune system. Immunotherapy works by removing the signals that prevent immune cells from attacking cancer, helping the body better identify and destroy any remaining cancer cells after surgery.

Cure: The study found that adding immunotherapy reduced the risk of the cancer coming back or causing death by about 50%. How should patients understand that number — what does it actually mean for someone worried about recurrence?

Sinicrope: In this study, patients received either chemotherapy alone or chemotherapy plus immunotherapy. The group that received immunotherapy had about a 50% lower risk of recurrence or death, which represents a very large benefit in this setting. Based on the survival data, many patients treated with the combination approach may be cured of their disease. Overall, this regimen appears to be significantly more effective than chemotherapy alone.

At three years, more patients stayed cancer-free with the addition of immunotherapy (86.3% vs 76.2%). Why is that difference considered such an important step forward in colon cancer treatment?

This level of improvement is notable because similar gains have not been seen in prior adjuvant colon cancer trials. Many earlier studies testing targeted therapies in early-stage disease did not improve outcomes. In contrast, this study shows a meaningful increase in the number of patients who remain cancer-free. The benefit is both clinically significant and relatively uncommon in this treatment setting, making it an important advance.

One of the most important parts of this study is that it only applies to patients with dMMR tumors. Why is testing for MMR status so critical right after diagnosis, and what could patients miss if they don’t get this testing?

Testing for mismatch repair (MMR) status is essential because it identifies patients who are most likely to benefit from immunotherapy. It is now recommended for all patients diagnosed with colon or rectal cancer. This testing can also detect Lynch syndrome, a hereditary condition linked to multiple cancers. Without MMR testing, patients may miss the opportunity to receive immunotherapy, which can lead to better outcomes than chemotherapy alone in this specific group.

What should patients know about the safety of adding immunotherapy to chemotherapy? How do the side effects compare, and how are immune-related side effects typically managed?

Adding immunotherapy does increase some side effects, but most are manageable and consistent with what is already known about these treatments. The most common immune-related side effect observed was mild hypothyroidism. Importantly, severe immune-related side effects were not significantly increased. Overall, the treatment was considered fairly well tolerated, and side effects can typically be managed with standard monitoring and care.

For a patient newly diagnosed today with stage III colon cancer, how should these results change the conversation with their doctor? What should they be asking to make sure they’re getting the most appropriate and up-to-date treatment?

Patients should ask whether their tumor has been tested for mismatch repair status, as about 10% to 15% of colon cancers have this abnormality. If a tumor is dMMR, immunotherapy may be a more effective option than chemotherapy alone. These findings highlight the importance of personalized treatment decisions and ensuring that testing is done early so the most appropriate therapy can be selected.

Transcript edited for clarity an conciseness

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