Dr Sinicrope on the Efficacy and Safety of mFOLFOX6 Plus Atezolizumab in Stage III dMMR CRC

"The combination of mFOLFOX6 and atezolizumab resulted in a 50% reduction in recurrence or death in patients [with dMMR CRC] compared with mFOLFOX6 alone. We regard that as a very clinically meaningful difference, and believe that this trial is practice changing."

Frank A. Sinicrope, MD, a gastroenterologist, internist, and oncologist at Mayo Clinic, shared efficacy and safety findings from the phase 3 ATOMIC trial (NCT02912559), which evaluated the addition of atezolizumab (Tecentriq) to adjuvant mFOLFOX6 (modified oxaliplatin, leucovorin, and fluorouracil) in patients with stage III, mismatch repair–deficient (dMMR) colon cancer.

Data presented at the 2025 ASCO Annual Meeting showed that the combination of atezolizumab plus mFOLFOX6 led to a statistically significant improvement in disease-free survival (DFS) compared with mFOLFOX6 alone. At the second interim analysis, conducted after 75% of DFS events had occurred, the trial met the prespecified boundary for efficacy. At a median follow-up of 37.2 months (Q1-Q3, 24.2-55.7) and a data cutoff February 4, 2025, the 3-year DFS rate was 86.4% with atezolizumab plus chemotherapy (n = 346) vs 76.6% with chemotherapy alone (n = 334), translating to a 50% reduction in the risk of recurrence or death (HR, 0.50; 95% CI, 0.34-0.72; P < .0001). Sinicrope stated that these results are “clinically meaningful” and support the adoption of this regimen as a new standard of care for patients with stage III dMMR colon cancer. He also noted that the DFS curve in the combination arm was plateauing, suggesting durable benefit and a lack of continued recurrence over time.

The addition of atezolizumab to mFOLFOX6 resulted in a manageable safety profile consistent with the known toxicities of each agent. The most notable difference was a higher rate of grade 4 neutropenia in the combination arm, which was non-febrile and considered clinically manageable. Sinicrope emphasized that the incidence of neutropenia in the control arm was lower than what has been reported in historical trials using mFOLFOX6, further supporting the tolerability of the combination, he added.

These findings position adjuvant atezolizumab plus mFOLFOX6 as a practice-changing regimen for patients with stage III dMMR colon cancer, Sinicrope concluded.