Atezolizumab Plus Chemotherapy Improves DFS in dMMR Colon Cancer

The addition of atezolizumab (Tecentriq) to standard adjuvant chemotherapy significantly improved disease-free survival (DFS) in patients with resected stage III colon cancer with deficient DNA mismatch repair (dMMR), according to results from the phase 3 ATOMIC trial (Alliance A021502; NCT02912559). The findings support the incorporation of chemoimmunotherapy into the adjuvant setting for this molecularly defined subgroup and may inform updates to clinical practice guidelines.^1,2

In the randomized, multicenter trial, the addition of the PD-L1 inhibitor atezolizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX) reduced the risk of recurrence or death by approximately 50% compared with chemotherapy alone. At 3 years, the DFS rate was 86.3% in the atezolizumab-containing arm vs 76.2% with FOLFOX alone (HR, 0.50; 95% CI, 0.35-0.73; P <.001).

“Despite millions of new colorectal cancer diagnoses each year, many patients—especially those with advanced disease—still have limited treatment choices,” Eileen O’Reilly, MD, from Memorial Sloan Kettering Cancer Center and Jeffrey Meyerhardt, MD, MPH, from Dana-Farber Cancer Institute, who co-chair the Gastrointestinal Committee for the Alliance, stated in a news release.¹ “The ATOMIC trial suggests a new direction: combining chemotherapy with immunotherapy to enlist the body’s own immune system in the fight against cancer. This approach could offer patients a significantly more powerful path forward.”

These data derive from 712 patients enrolled between 2017 and 2023 following surgical resection of stage III dMMR colon cancer. Participants were randomly assigned to receive 6 months of adjuvant FOLFOX with or without concurrent atezolizumab, followed by an additional 6 months of atezolizumab monotherapy in the investigational arm. The primary end point was DFS, with overall survival (OS) and safety as key secondary endpoints.³

The magnitude and consistency of benefit observed across prespecified subgroups underscore the biologic rationale for integrating immune checkpoint blockade in dMMR tumors, which are characterized by high microsatellite instability and increased neoantigen burden. Prior to ATOMIC, immunotherapy had demonstrated efficacy primarily in the metastatic setting for dMMR colorectal cancer, with limited evidence supporting its use in earlier-stage disease.

The safety profile of the combination regimen was consistent with known toxicities of both FOLFOX and atezolizumab. Immune-related adverse events were observed but were generally manageable, and no new safety signals emerged. Rates of grade 3 or higher adverse events were higher in the combination arm at 84.1% vs 71.9% in control arm, reflecting the addition of immunotherapy, but did not appear to compromise overall treatment delivery.

The ATOMIC trial addresses an unmet need in stage III colon cancer, where standard adjuvant chemotherapy has provided incremental benefit but remains insufficient for a subset of patients. Approximately 10% to 15% of colon cancers exhibit dMMR status, a biomarker associated with resistance to fluoropyrimidine-based therapy and sensitivity to immune checkpoint inhibition.

The findings also reinforce the importance of routine mismatch repair testing at diagnosis. Identification of dMMR status not only has implications for Lynch syndrome screening but also directly informs treatment selection, particularly as immunotherapy moves into earlier lines of therapy.

While OS data remain immature, the observed DFS benefit is clinically meaningful and aligns with regulatory and guideline precedents supporting DFS as a surrogate endpoint in the adjuvant colon cancer setting. Ongoing follow-up will clarify the durability of benefit and potential impact on long-term survival outcomes.

The trial was conducted by the Alliance for Clinical Trials in Oncology, part of the National Cancer Institute–funded National Clinical Trials Network, in collaboration with international partners. Results have been presented at the American Society of Clinical Oncology Annual Meeting and are expected to inform future updates to treatment guidelines.

“From a statistical standpoint, the results of Alliance A021502 are compelling,” Fang-Shu Ou, PhD, associate professor of Biostatistics at Mayo Clinic, and lead biostatistician on ATOMIC, stated in the news release.¹ “The data indicate a clear, statistically significant improvement in patient outcomes, with minimal variability. The strength of the evidence is robust, and the findings strongly support the potential for this treatment to make a meaningful difference in clinical practice."

REFERENCES

1. Alliance for Clinical Trials in Oncology. ATOMIC trial press release, March 2026. Available at: https://tinyurl.com/4dhwpbhw

2. Sinicrope FA, Ou FS, Arnold D, et al. Atezolizumab plus FOLFOX for stage III mismatch repair-deficient colon cancer. N Engl J Med. 2026;394(12):1155-1166. doi:10.1056/NEJMoa2507874

3. Testing the addition of atezolizumab to adjuvant chemotherapy in stage III colon cancer (ATOMIC). ClinicalTrials.gov. https://tinyurl.com/4r3uzbxr