{
  "abstract": "Background Stage III colon cancers with deficient DNA mismatch repair (dMMR) are relatively chemoresistant yet highly immunogenic. ATOMIC is the first cooperative-group study to test whether adding PD-L1 blockade to standard adjuvant chemotherapy improves outcomes in this biomarker-defined population.Methods In this international, open-label, randomized phase III trial, 712 patients with resected stage III dMMR colon cancer were assigned 1:1 to receive 12 cycles of mFOLFOX6 alone (control) or mFOLFOX6 plus atezolizumab 840 mg Q2W for 12 cycles followed by atezolizumab monotherapy Q3W for 13 cycles (experimental). The primary end-point was disease-free survival (DFS); key secondaries included overall survival (OS), safety, and predefined translational correlative analyses (tumour mutational burden [TMB], IFN-γ gene signature, baseline gut microbiome). The second interim analysis (75% of DFS events) was triggered at 37.2 months’ median follow-up.Results DFS: 3-year DFS was 86.4% (95% CI 81.8–89.9) with atezolizumab + mFOLFOX6 vs 76.6% (95% CI 71.3–81.0) with mFOLFOX6 alone (HR 0.50, 95% CI 0.35–0.72; P < 0.0001), representing a 50% relative reduction in recurrence or death (table 1).Subgroups: DFS benefit was consistent across age ≥ 70 y, sex, tumour location, and high-risk T4/N2 disease (all HR ≤ 0.60; interaction P > 0.10).Safety: Grade ≥ 3 treatment-related adverse events occurred in 71.7% vs 62.1% of patients in the experimental and control arms, respectively; immune-related AEs were infrequent (4.2%) and manageable (table 1).OS: Data remains immature; a positive trend has emerged (HR 0.79) and further follow-up is ongoing.Correlative science: preliminary analyses show (i) higher baseline TMB correlates with longer DFS in both arms, with greatest absolute benefit in the top quartile; (ii) an elevated IFN-γ signature enriches for atezolizumab benefit; (iii) dominance of Ruminococcus species in pretreatment stool samples associates with favorable DFS. Final assays and integrated biomarker model will be reported.Conclusions Adding atezolizumab to adjuvant mFOLFOX6 doubled the proportion of patients alive and recurrence-free at three years, establishing the first practice-changing adjuvant chemo-immunotherapy regimen for stage III dMMR colon cancer. These data support routine MMR testing and adoption of chemo-immunotherapy in this subgroup while biomarker work continues to refine patient selection and identify candidates for treatment de-escalation.Abstract 495 Table 1Efficacy and safety outcomes for Atezolizumab + mFOLFOX6 Abbreviations: HR = hazard ratio; CI = confidence interval; AE = adverse event; mo = months; pp = percentage points",
  "authors": [
    {
      "affiliations": [
        "Northeast Georgia Medical Center, Atlanta, GA, USA"
      ],
      "name": "Chiugo Okoye"
    },
    {
      "affiliations": [
        "Northeast Georgia Medical Center, Gainesville, GA, USA"
      ],
      "name": "Adeoluwa Adewuyi"
    },
    {
      "affiliations": [
        "UAMS Northwest Arkansas, Fayetteville, AR, USA"
      ],
      "name": "Chinemerem M Emeasoba"
    },
    {
      "affiliations": [
        "Trinity Health Ann Arbor, Ypsilanti, MI, USA"
      ],
      "name": "Olanipekun Ntukidem"
    }
  ],
  "title": "495 Breaking the recurrence barrier in colon cancer: ATOMIC trial doubles disease-free survival with atezolizumab+mFOLFOX6",
  "uid": "c8b948bc-2d39-5795-983c-8139864739fe"
}