Patients with surgically resected stage III mismatch repair deficient (dMMR) colon cancer had a 50% reduction in disease recurrence or death when treated with adjuvant chemoimmunotherapy compared to those treated with chemotherapy alone.
Standard treatment of stage III colon cancer (node-positive) consists of surgical resection followed by chemotherapy with fluoropyrimidine and oxaliplatin (FOLFOX).1 Around 15% of colon cancers have deficient mismatch repair (dMMR) genes and may display resistance to chemotherapy.2,3 It is unknown whether an immune checkpoint inhibitor can improve outcomes after surgical resection of stage III dMMR colon cancer. At ASCO 2025, the results of the ATOMIC trial were presented.4
The multi-centre, open-label, phase III ATOMIC study enrolled patients (≥12 years old) with surgically resected (R0) stage III dMMR colon adenocarcinoma (any T, N1-2, M0). Both sporadic and Lynch syndrome-associated patients were eligible. Patients could not have received prior chemotherapy or radiation, however, one cycle of mFOLFOX6 prior to randomisation was permitted. Within 10 weeks post-surgery, patients were randomised 1:1 to receive either mFOLFOX6 for 6 months, or mFOLFOX6 plus atezolizumab for 6 months followed by 6 months of atezolizumab. The primary endpoint was disease-free survival (DFS). Key secondary endpoints included overall survival (OS) and safety.
A total of 712 patients were enrolled and randomised to mFOLFOX6 plus atezolizumab (N= 355) and mFOLFOX6 (N= 357). In the mFOLFOX6 plus atezolizumab arm, 46.2% of patients completed treatment per protocol compared to 59.7% in the mFOLFOX6 arm. Baseline patient characteristics were well balanced between study arms, including the proportion of T4 (~32%) and N2 (~37%) tumours.
At a median follow-up of 37.2 months, 3-year DFS was 86.4% with mFOLFOX6 plus atezolizumab compared to 76.6% with mFOLFOX6 alone (HR[95% CI]: 0.50[0.34-0.72], log-rank p< 0.0001). The benefit was consistent across subgroups. OS data are not yet mature.
Grade 3-4 treatment-related adverse events (TRAEs) occurred in 72.3% of patients in the mFOLOFOX6 plus atezolizumab arm compared to 59.2% in the mFOLFOX6 arm. Grade 5 TRAEs occurred in 0.6% of patients (N= 2, 1 sudden death and 1 sepsis) in the mFOLOFOX6 plus atezolizumab arm compared to 0% in the mFOLOFX6 arm. The most common grade 3-4 adverse events (AEs) in the mFOLFOX6 plus atezolizumab arm were neutrophil count decreased (43%), peripheral sensory neuropathy (19%), and diarrhoea (12%). No clinically significant differences in grade 3-4 immune-related AEs were observed between both study arms.
The addition of atezolizumab to standard mFOLFOX6 chemotherapy reduced the risk of recurrence or death by 50% compared to chemotherapy alone. These data support adjuvant atezolizumab plus mFOLFOX6 as a potential new standard of care for patients with surgically resected stage III dMMR colon cancer.
References
1. Argilés G, Tabernero J, Labianca R, et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020;31(10):1291-305.
2. Gutierrez C, Ogino S, Meyerhardt JA, Iorgulesco JB. The prevalence and prognosis of microsatellite instability-high/mismatch repair-deficient colorectal adenocarcinomas in the United States. JCO Precis Oncol 2023;e2200179.
3. Sinicrope FA, Sargent DJ. Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications. Clin Cancer Res 2012;18(6):1506-12.
4. Sinicrope FA, Ou FS, Arnold D, et al. Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer (Alliance A021502; ATOMIC). Presented at ASCO 2025; Abstract LBA1.
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