Results from the international phase III ATOMIC study demonstrated that patients with deficient mismatch repair (dMMR) colon cancer who receive atezolizumab in addition to adjuvant chemotherapy experience a 50% reduction in disease recurrence or death compared with chemotherapy alone. The findings are being presented during the Plenary Session at the 2025 ASCO Annual Meeting (Abstract LBA1).
Colorectal cancer is the third most commonly diagnosed cancer worldwide. Approximately one-third of patients will have stage III disease at diagnosis, and between 10% and 15% of these tumors have deficient DNA mismatch repair (dMMR).
“Colon cancers with deficient mismatch repair have shown relative resistance to chemotherapy. However, these tumors show a high burden of mutations [that] are immunogenic and can lead to stronger anti-tumor immune responses when treated with immunotherapy,” noted lead study author Frank A. Sinicrope, MD, of Mayo Clinic, Rochester, Minnesota.
Study Methods
The multicenter, randomized, phase III ATOMIC trial was conducted to determine whether atezolizumab, an anti–PD-L1 antibody, can improve outcomes when added to adjuvant mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin), the current standard of care, in patients with surgically resected stage III dMMR tumors.
The study enrolled a total of 712 patients with a median age of 64 years, approximately half of whom were female. Patients were randomly assigned to receive mFOLFOX6 plus atezolizumab at 840 mg intravenously every 2 weeks for 12 cycles followed by atezolizumab monotherapy for 13 cycles (n = 355) vs mFOLFOX6 alone for 12 cycles (n = 357). The primary endpoint was disease-free survival, and secondary endpoints were overall survival and adverse event profile.
Results
At a median follow-up of 37.2 months, 124 out of 712 patients experienced a disease-free survival event of cancer recurrence or death. The 3-year disease-free survival was 86.4% (95% confidence interval [CI] = 81.8%–89.9%) in the atezolizumab arm and 76.6% (95% CI = 71.3%–81.0%) in the mFOLFOX6 arm (hazard ratio = 0.50; 95% CI = 0.35%–0.72%).
Patients treated with atezolizumab plus mFOLFOX6 had a 50% lower risk of recurrence and death compared with patients treated with mFOLFOX6 alone. Furthermore, efficacy for atezolizumab was consistent across subgroups, including patients older than 70 years, low-risk patients, and high-risk patients.
Treatment-related grade ≥ 3 adverse events occurred in 71.7% of patients in the atezolizumab arm vs 62.1% in the mFOLFOX6 arm, but these were manageable and consistent with the known toxicities of the drugs.
Conclusions and Next Steps
“This study will change the standard of care for the subset of patients with [dMMR] colon cancer,” remarked Joel Saltzman, MD, Vice Chair of Regional Oncology at Taussig Cancer Center, Cleveland Clinic, and an ASCO Expert in gastrointestinal cancers. “A study like this could never be completed without the multicenter structure of a cooperative group trial that has National Cancer Institute funding, given the small percentage of patients with this distinct form of colon cancer."
The trial is ongoing, and patients will continue to be followed. Study investigators plan on studying biospecimens from the trial to identify biomarkers that may predict which patients are more likely to receive benefit from the chemoimmunotherapy regimen, as well as who might be at a higher risk of cancer recurrence.
Disclosure: This study was funded by the National Cancer Institute and Genentech. For full disclosures of the study authors, visit coi.asco.org.
