Biomarker Modulation by Aspirin and Metformin for Colorectal Cancer Prevention: Results from the ASAMET Randomized Phase II Trial.
Irene M Briata, Alessio Carbone, Sebastian Foersch et al.
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In 30 seconds
The multicenter, double-blind, 2 × 2 factorial phase II ASAMET randomized trial evaluated aspirin, metformin, and their combination for 12 months in patients with resected stage I to III colorectal cancer. Among 51 participants, metformin reduced global NF-κB expression in normal colorectal mucosa compared with placebo (-9.04 [95% CI, -17.55 to -0.54; P = 0.04]); aspirin alone did not. The combination showed a nonsignificant reduction. Ki67 and pS6K were unchanged globally, and no serious adverse events occurred.
Key findings
- Metformin reduced global mucosal NF-κB versus placebo by -9.04 [95% CI, -17.55 to -0.54; P = 0.04].
- Pooled analysis showed a metformin-driven NF-κB effect (Met vs. non-Met: -7.29; 95% CI, -13.79 to -0.79; P = 0.03); aspirin had no impact (P = 0.73).
- Global Ki67 and pS6K were unchanged; the aspirin–metformin combination increased right-sided Ki67 (12.48; 95% CI, 0.45-24.51; P = 0.04).
- Toxicity was manageable, with no serious adverse events.
Why it matters
The findings provide randomized evidence that metformin can modulate NF-κB in histologically normal colorectal mucosa after colorectal cancer resection, supporting a potential biological mechanism for secondary prevention. The absence of favorable biomarker effects with aspirin in this study and the lack of change in other global markers underscore the need to distinguish biomarker modulation from demonstrated prevention of cancer recurrence or new cancers.
What to keep in mind
This phase II trial included 51 patients and assessed tissue biomarkers over 12 months; it does not establish an effect on colorectal cancer recurrence or incidence.