The findings from the phase III ATOMIC trial (NCT02912559) were presented during the Plenary Session at the ASCO 2025 (#Abstract LBA1). This phase III study is funded by the National Cancer Institute and Genentech. The ATOMIC study was designed to investigate whether adding immunotherapy with TECENTRIQ (atezolizumab) to standard adjuvant chemotherapy [FOLFOX6 (fluorouracil, leucovorin, and oxaliplatin)] improves outcomes for patients with stage III MSI-high colon cancer. This study has provided insights into several key questions:

- Is chemotherapy necessary for all patients?

- What is the optimal duration of chemotherapy?

- Should patients be exposed to treatment for more than six months, considering findings from neoadjuvant studies?

- Will there be a significant overall survival (OS) benefit with this approach?

The ATOMIC trial enrolled 712 patients with resected stage III colon cancer and confirmed dMMR via immunohistochemistry, across over 300 National Clinical Trials Network sites. Eligible participants had not received prior chemotherapy or radiation and had an ECOG performance status of 2 or lower. Following surgery, patients were randomized to receive either atezolizumab combined with standard mFOLFOX6, followed by 6 months of atezolizumab, or mFOLFOX6 alone. The trial’s primary endpoint was DFS, with secondary endpoints including overall survival and safety.

Findings from ASCO 2025 suggests that this study could change the landscape of patients with mismatch repair–deficient/microsatellite instability-high stage III, and potentially high-risk stage II, colon cancer in the adjuvant setting. 

As of the February 4, 2025 data cutoff, with a median follow-up of 37.2 months, the second interim analysis, conducted at 75% of disease-free survival (DFS) events—showed that the trial met its pre-specified efficacy threshold, prompting data release.

At the 3-year mark, DFS was significantly higher in the atezolizumab plus chemotherapy arm at 86.4% compared to 76.6% with chemotherapy alone. The DFS curve had begun to plateau, suggesting a sustained absence of recurrence or death in the combination arm.

Compared to patients treated with mFOLFOX6 alone, people treated with atezolizumab with mFOLFOX6 had a 50% decreased risk of death and recurrence. Additionally, atezolizumab's effectiveness was consistent across subgroups, such as people over 70, low-risk patients, and high-risk patients.

Compared to 62.1% in the mFOLFOX6 arm, 71.7% of patients in the atezolizumab arm experienced treatment-related grade 3 and higher adverse events; nevertheless, these were controllable and in line with the drugs' known toxicities.

KOL insights

This study will change the standard of care (SOC) for patients with resected dMMR/MSI-H colon cancer. – Expert Opinion

In Europe, however, oncologists often use three months of chemotherapy rather than six, especially for lower-risk patients. It was suggested that in practice, chemotherapy duration might be shortened to three months while continuing immunotherapy for a full year.– Expert Opinion

Conclusion

About 10-15% of stage III colon cancers are dMMR tumors. These tumors are less responsive to chemotherapy but often respond well to immunotherapy, as seen in rectal cancer trials. Neoadjuvant immunotherapy has demonstrated remarkable success in treating rectal dMMR/MSI tumors, but it has yet to become a standard approach for colon cancer.  Until now, immune checkpoint inhibitors were only approved for metastatic (stage IV) colorectal cancer. 

The ATOMIC trial marks a pivotal advancement in the adjuvant treatment of stage III dMMR colon cancer, establishing the combination of atezolizumab with mFOLFOX6 as a new standard of care. With a significant improvement in 3-year DFS and consistent benefit across subgroups, along with a manageable safety profile, this study not only reinforces the role of immunotherapy in early-stage colon cancer but also sets the stage for a shift in clinical practice.

There are still several unanswered questions regarding atezolizumab treatment. One key uncertainty is whether all patients require the full 12-month treatment course or if a shorter duration could be equally effective. Regional treatment practice differences could be another challenge. In Europe, it is common practice to use 3 months of adjuvant chemotherapy, particularly in low-risk patients. The findings from ATOMIC raise the possibility of a shortened chemotherapy duration combined with a full year of atezolizumab, which could offer a more tolerable yet effective regimen—though this approach will require validation in future studies. 

In addition to this, identifying reliable biomarkers to determine which patients benefit most from atezolizumab is crucial, as this could help reduce toxicity and prevent overtreatment. Furthermore, OS data is still pending, leaving uncertainty about the long-term impact of atezolizumab on patient prognosis. OS data insights are very important given the cost implications of adjuvant immuno-oncology (IO) therapy. These gaps highlight the need for further research to refine treatment strategies and improve patient outcomes.