Dr Sinicrope on the Clinical Implications of the ATOMIC Trial for Stage III dMMR CRC

"With the ATOMIC trial, we have data showing that the addition of immunotherapy to chemotherapy can significantly benefit this patient population. Practitioners will be very eager to implement this regimen into their clinical practice."

Frank A. Sinicrope, MD, coleader of the Gastrointestinal Cancer Program and clinical investigator at Mayo Foundation, discussed the implications of the phase 3 ATOMIC trial (NCT02912559) for clinical practice in stage III, mismatch repair–deficient (dMMR) colon cancer.

At the 2025 ASCO Annual Meeting, results from the trial demonstrated a statistically significant disease-free survival (DFS) benefit with the addition of atezolizumab (Tecentriq) to standard adjuvant mFOLFOX6 (modified oxaliplatin, leucovorin, and fluorouracil) chemotherapy for this patient population.

At a median follow-up of 37.2 months (Q1-Q3, 24.2-55.7) , the 3-year DFS rate was 86.4% with atezolizumab plus mFOLFOX6 (n = 346) compared with 76.6% with mFOLFOX6 alone (n = 334). This corresponded to a 50% reduction in the risk of disease recurrence or death (HR, 0.50; 95% CI, 0.34-0.72; P < .0001). The second interim analysis met the prespecified boundary for efficacy after 75% of DFS events had occurred. The data cutoff was February 4, 2025.

Sinicrope emphasized that although dMMR colon cancer is relatively chemoresistant, this population is known to respond well to immune checkpoint inhibition in the metastatic setting. Until now, data supporting the use of immunotherapy in earlier-stage disease had been lacking, he stated. Findings from ATOMIC now provide the first evidence that immune checkpoint inhibition can improve DFS in the adjuvant setting for patients with stage III dMMR colon cancer, Sinicrope asserted, adding that this represents a potential practice-changing development.

Given the strength of the data, Sinicrope noted that guideline committees are being approached to review the findings for potential inclusion in future treatment recommendations. With updated guidance, oncologists may increasingly adopt adjuvant atezolizumab plus mFOLFOX6 as a new standard for this biologically distinct subset of patients, he concluded.