The phase 3 ATOMIC trial demonstrated a statistically and clinically significant improvement in survival outcomes with the addition of atezolizumab to standard mFOLFOX6 chemotherapy and a manageable safety profile for patients with resected stage III deficient mismatch repair (dMMR) colon cancer.

These results will first be presented by Frank Sinicrope, MD, Mayo Clinic Rochester, Rochester, Minnesota, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

The benefit of an immune checkpoint inhibitor combined with standard adjuvant chemotherapy (fluoropyrimidine plus oxaliplatin) remains unknown for patients with stage 3 colon cancer and dMMR. To address this, researchers conducted a multicenter, randomized phase 3 clinical trial to evaluate the clinical benefit of an anti-PD-L1 antibody, atezolizumab, with adjuvant 5-fluorouracil, leucovorin plus oxaliplatin (mFOLFOX6).

Patients were randomized 1 to 1 to receive either mFOLFOX6 alone for 12 cycles or mFOLFOX6 plus atezolizumab (840 mg IV every 2 weeks) for 12 cycles followed by atezolizumab monotherapy for an additional 13 cycles. Patients were stratified by nodal status (N₁/N_1c vs N₂), T-stage (T₁ to T₃ vs T₄), and tumor location (proximal vs distal).

The primary end point was disease-free survival (DFS), and secondary end points were overall survival (OS) and safety.

Overall, 712 patients diagnosed with resected stage III dMMR colon adenocarcinoma between September 2017 and January 2023 were included. The median age was 64 years and 45.9% were male. The median follow up for all patients was 37.2 months, and DFS events were identified at second analysis. Patients who were treated with atezolizumab plus mFOLFOX6 (n = 355) had a higher 3-year DFS rate than patients treated with mFOLFOX6 alone (86.4%; 95% confidence interval [CI], 81.8 to 89.9 vs 76.6%; 95% CI, 71.3 to 81; hazard ratio [HR] 0.50; 95% CI, 0.35 to 0.72; P  <.0001).

Benefit with atezolizumab was consistent across prespecified subgroups, including patients over age 70 and those with both low-risk (T₁ to T₃, N₁/N_1c) and high-risk (T₄or N₂) disease.

In terms of safety, grade ≥3 treatment-related adverse events were more frequent in the additional atezolizumab group than the mFOLFOX6 alone group (71.7% vs 62.1%).

"The addition of atezolizumab to mFOLFOX6 significantly improved DFS and should be considered the new adjuvant standard of care for patients with dMMR stage III colon cancer," the researchers concluded.

Source:

Sinicrope F, Ou F, Arnold DA, 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 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA1.