ATOMIC trial establishes new standard for adjuvant treatment in dMMR stage 3 colon cancer

Atezolizumab plus chemotherapy significantly reduced the risk of death or recurrence by 50% compared with chemotherapy alone for patients with stage 3 colon cancer characterised by deficient DNA mismatch repair (dMMR).

Prof. Frank Sinicrope (Mayo Clinic, Rochester, MN, USA) presented this second interim analysis of the phase 3 ATOMIC trial (NCT02912559) [1]. The study enrolled 712 patients with resected stage 3 dMMR colon cancer. Eligible patients had no prior chemotherapy or radiotherapy and an ECOG performance status of 0–2. Following surgery, participants were randomised to receive either standard chemotherapy with mFOLFOX6 alone (oxaliplatin, leucovorin calcium, and fluorouracil) or the same regimen in combination with atezolizumab, followed by 6 months of atezolizumab monotherapy. The primary outcome was to assess whether the combination regimen could significantly improve disease-free survival (DFS) compared with FOLFOX alone in this patient population.

The second interim analysis confirmed a significant DFS benefit, meeting the primary outcome. At a median follow-up of 37.2 months, the combination therapy achieved a 3-year DFS rate of 86.4%, compared with 76.6% for chemotherapy alone (HR 0.50; 95% CI 0.34–0.72; P<0.0001). “This is a substantial DFS benefit,” said Prof. Sinicrope. “The DFS curve is plateauing, indicating that we’re not seeing any more recurrences or deaths with the immunotherapy and chemotherapy combination.”

Subgroup analyses confirmed consistent benefit across key clinical and demographic variables. DFS favoured the combination arm in patients with both proximal (HR 0.56; 95% CI 0.38–0.83) and distal tumours (HR 0.31; 95% CI 0.11–0.87), across T-stage (Tx/T1–3: HR 0.51; 95% CI 0.31–0.85; T4: HR 0.46; 95% CI 0.27–0.79), and in both low- and high-risk disease groups (low-risk: HR 0.47; 95% CI 0.24–0.94; high-risk: HR 0.51; 95% CI 0.33–0.78). “No matter the patient’s age, sex, race, tumour location, or T-stage, patients are doing better with the addition of immunotherapy,” Prof. Sinicrope added.

The safety profile was consistent with previous experience with each agent, with a manageable increase in non-febrile neutropenia observed in the combination arm. “This data establishes this combination as a new standard treatment for patients with stage 3 colon cancer and dMMR,” said Prof. Sinicrope. The data suggests a practice-changing benefit, marking the first successful adjuvant immunotherapy trial in this setting.

Commenting on the broader implications on behalf of ASCO, Dr Joel Saltzman (Cleveland Clinic, OH, USA), stated: “This study involves a real-world population that I see in my clinic. We’ve believed immunotherapy could help in this setting, but didn’t know how to integrate it.”

1. Sinicrope F. 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). Abstract LBA1, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.

Medical writing support was provided by Dr Rachel Giles.
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Posted on 3 June 2025