As reported in The New England Journal of Medicine by Sinicrope et al, the phase III ATOMIC trial has shown that the addition of adjuvant atezolizumab to mFOLFOX6 (modified fluorouracil, oxaliplatin, and leucovorin) improved disease-free survival in patients with resected stage III mismatch repair–deficient (dMMR) colon cancer.
Study Details
In the U.S./German trial, 712 patients were enrolled at 303 National Clinical Trials Network sites and 9 Arbeitsgemeinschaft Internistische Onkologie sites between September 2017 and January 2023. Patients were randomly assigned to adjuvant atezolizumab at 840 mg every 2 weeks for 12 cycles for 6 months plus mFOLFOX6 for 12 cycles for 6 months total, followed by atezolizumab monotherapy for 13 cycles for 12 months total (n = 355) or mFOLFOX6 alone for 12 cycles for 6 months total. A total of 53.9% patients had high-risk tumors (T4, N2, or both). The primary endpoint was disease-free survival.
Key Findings
Median follow-up for disease-free survival was 40.9 months (interquartile range [IQR] = 26.7–58.6 months). Disease-free survival at 3 years was 86.3% (95% confidence interval [CI] = 81.8%–89.8%) in the atezolizumab/mFOLFOX6 group vs 76.2% (95% CI = 70.9%–80.6%) in the mFOLFOX6 group (hazard ratio [HR] = 0.50, 95% CI = 0.35–0.73, P < .001). HRs were 0.41 (95% CI = 0.27–0.64) among patients who received more than six cycles of mFOLFOX6 and 0.97 (95% CI = 0.44–2.11) among those who received six or fewer cycles.
Median follow-up for overall survival was 45.8 months (IQR = 32.0–64.7 months). Death occurred in 31 patients in the atezolizumab/mFOLFOX6 group vs 33 patients in the mFOLFOX6 group (P = 0.68). Overall survival at 5 years was 89.7% (95% CI = 85.2%–92.9%) in the atezolizumab/mFOLFOX6 group vs 87.9% (95% CI = 83.1%–91.4%) in the mFOLFOX6 group (HR = 0.90, 95% CI = 0.55–1.47).
Grade 3 to 4 adverse events occurred in 84.1% of the atezolizumab/mFOLFOX6 group vs 71.9% of the mFOLFOX6 group. The most common were decreased neutrophils (43.6%), peripheral sensory neuropathy (18.5%), and fatigue (10.1%) vs decreased neutrophils (35.9%), peripheral sensory neuropathy (15.0%), and hypertension (11.7%). Two deaths in the atezolizumab/mFOLFOX6 group were considered related to treatment (due to sudden death and sepsis).
The investigators concluded: “The addition of atezolizumab to mFOLFOX6 significantly improved disease-free survival among patients with stage III dMMR colon cancer.”
Frank A. Sinicrope, MD, of Mayo Clinic, Rochester, Minnesota, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was funded by the National Cancer Institute and Genentech. For full disclosures of the study authors, visit nejm.org.
