Atezolizumab Plus FOLFOX Improves DFS in Stage III dMMR Colon Cancer

Key Takeaways

• The phase 3 randomized trial compared atezolizumab plus mFOLFOX6 with mFOLFOX6 alone after resection in stage III dMMR colon cancer.
• Disease-free survival was higher and recurrence or death was lower with the atezolizumab-containing regimen at the reported follow-up.
• Grade 3 or 4 adverse events were more frequent with the combination, and overall survival remained a secondary endpoint.

In resected stage III mismatch repair–deficient colon cancer, adding atezolizumab to adjuvant mFOLFOX6 was associated with higher 3-year disease-free survival than mFOLFOX6 alone in ATOMIC Alliance A021502. The 3-year rate was 86.3% with the combination and 76.2% with chemotherapy alone. This phase 3 randomized trial evaluated postoperative therapy in a molecularly defined stage III population after curative-intent surgery. It tested whether adding checkpoint blockade to the chemotherapy backbone would improve the primary endpoint of disease-free survival.

The trial randomly assigned 712 patients in a 1:1 ratio overall, with 355 receiving atezolizumab plus mFOLFOX6 and 357 receiving mFOLFOX6 alone. Treatment consisted of atezolizumab plus mFOLFOX6 for 6 months, followed by atezolizumab alone to complete 12 months, or mFOLFOX6 alone for 6 months. The median age was 64 years, 55.1% of participants were women, and 53.9% had T4 disease, N2 disease, or both as baseline higher-risk features. Disease-free survival was the primary endpoint, while overall survival and the adverse-event profile were prespecified secondary endpoints.

Median follow-up was 40.9 months in the randomized population overall. At that analysis, the hazard ratio for disease recurrence or death was 0.50 with combination therapy. The 95% confidence interval ranged from 0.35 to 0.73, and the reported P value was less than 0.001. These estimates aligned with the 86.3% and 76.2% 3-year disease-free survival rates, favoring the atezolizumab-containing regimen over chemotherapy alone.

Grade 3 or 4 adverse events occurred in 84.1% of patients who received atezolizumab plus mFOLFOX6 and 71.9% of those who received mFOLFOX6 alone. Overall survival remained a secondary endpoint at this analysis, alongside the adverse-event profile defined in the trial. The regimen improved disease-free survival at the reported follow-up while carrying a higher rate of grade 3 or 4 adverse events.