Adjuvant Atezolizumab/mFOLFOX6 Improves DFS in Stage III dMMR Colon Cancer

Atezolizumab (Tecentriq) plus mFOLFOX6 (fluorouracil, oxaliplatin, leucovorin) significantly improved disease-free survival (DFS) compared with mFOLFOX6 alone in patients with stage III mismatch repair-deficient (dMMR) colon cancer, according to findings from the phase 3 ATOMIC trial (NCT02912559) published in The New England Journal of Medicine and reported by the Alliance for Clinical Trials in Oncology.^1,2 This study represents the first phase 3 trial to evaluate the addition of an immune checkpoint inhibitor to standard adjuvant chemotherapy for this specific patient population.

Clinical Efficacy and Survival Outcomes

In the intent-to-treat population, with a median follow-up of 40.9 months (IQR, 26.7-58.6), patients receiving atezolizumab plus mFOLFOX6 achieved a 3-year DFS rate of 86.3% (95% CI, 81.8%-89.8%) compared with 76.2% (95% CI, 70.9%-80.6%) for those receiving mFOLFOX6 alone (HR, 0.50; 95% CI, 0.35-0.73; P <.001). An analysis of 630 patients with central confirmation of tumor dMMR status showed that the treatment effect was similar.

An analysis stratified by duration of mFOLFOX6 treatment revealed that DFS was improved with atezolizumab for patients who received more than 6 cycles of mFOLFOX6 (HR, 0.41; 95% CI, 0.27-0.64). Inversely, there was no observed advantage in the atezolizumab group when patients received 6 cycles or fewer of mFOLFOX6 (HR, 0.97; 95% CI, 0.44-2.11).

The overall survival (OS) analysis, with a median follow-up of 45.8 months (IQR, 32.0-64.7), showed that 31 patients had died in the atezolizumab group vs 33 patients who died in the mFOLFOX6 alone group. No significant OS difference was observed between the treatment arms (P = .68). Five-year OS rates were 89.7% (95% CI, 85.2%-92.9%) in the combination group and 87.9% (95% CI, 83.1%-91.4%) in the mFOLFOX6 alone group (HR, 0.90; 95% CI, 0.55-1.47).

It was also reported that there were 31 recurrences in the atezolizumab plus mFOLFOX6 group, of whom 24 received further systemic therapy, with 17 receiving immunotherapy.

Expert Commentary on the ATOMIC Findings

“The results of this study represent a pivotal advancement for the treatment of non-metastatic dMMR colon cancer,” stated Alliance Study Chair Frank A. Sinicrope, MD, professor of Oncology and clinical investigator of the Mayo Foundation at the Mayo Clinic Comprehensive Cancer Center, stated in the press release.² “The demonstrated improvement in outcomes supports a fundamental shift in how we approach adjuvant therapy for this molecular subgroup. These results provide compelling evidence that will inform and elevate the standard of care.”

Trial Breakdown and Study Design

The ATOMIC trial was a randomized, open-label, multicenter phase 3 study that enrolled 355 patients 12 years or older with completely resected stage III dMMR colon cancer. Patients were randomly assigned 1:1 to receive either the experimental combination or standard adjuvant chemotherapy. Eligibility criteria required an ECOG performance status from 0 to 2, and patients with Lynch syndrome were permitted to enroll. Those who had received prior chemotherapy or radiation therapy, except for 1 cycle of mFOLFOX6, were excluded from the study.

The treatment regimen for the control arm consisted of mFOLFOX6 administered every 14 days for 12 cycles. The mFOLFOX6 regimen included oxaliplatin at 85 mg/m², leucovorin at 400 mg/m², and a 5-fluorouracil bolus of 400 mg/m², followed by a 2400 mg/m² continuous infusion over 46 hours. Patients in the experimental arm received the same mFOLFOX6 schedule with the addition of atezolizumab at 840 mg administered intravenously every 2 The primary end point was DFS, with secondary end points including OS and safety.

Safety and Adverse Event Profile of Atezolizumab Plus mFOLFOX6

Grade 3 and 4 adverse events (AEs) occurred in 84.1% of patients in the atezolizumab plus mFOLFOX6 arm vs 71.9% in the mFOLFOX6 alone arm. Of grade 3 and 4 AEs, nonhematologic AEs occurred with a higher incidence in the combination group (69.4% vs 54.5%). The most common grade 3/4 toxicities across the atezolizumab group were decreased neutrophil count (43.6%), peripheral sensory neuropathy (18.5%), diarrhea (12.1%), and fatigue (10.1%). Treatment-related AEs (TRAEs) of grade 3 and 4 occurred in 72.5% of the combination group and 61.7% of the mFOLFOX6 alone group.

Grade 5 events occurred in 6 patients in the combination group and 2 in the mFOLFOX6 alone group. Investigators determined 2 of the deaths in the combination arm to be related to treatment, which were due to sudden death and sepsis.

“From a statistical standpoint, the results of Alliance A021502 are compelling,” added Fang-Shu Ou, PhD, an associate professor of Biostatistics at Mayo Clinic, and the lead biostatistician on ATOMIC.² “The data indicate a clear, statistically significant improvement in patient outcomes, with minimal variability. The strength of the evidence is robust, and the findings strongly support the potential for this treatment to make a meaningful difference in clinical practice.”

References

1. Sinicrope FA, Ou FS, Arnold D, et al. Atezolizumab plus FOLFOX for stage III mismatch repair-deficient colon cancer. N Engl J Med. 2026;394(12):1115-1126. doi:10.1056/NEJMoa2507874
2. Landmark Alliance ATOMIC trial establishes new standard of care for patients withstage III dMMR colon cancer. News release. Alliance for Clinical Trials in Oncology. March 25, 2026. Accessed March 26, 2026. https://tinyurl.com/3bv9687k