Aspirin Reduces Colorectal Cancer Recurrence in PI3K-Mutated Tumors
核心洞察
A daily 160mg dose of aspirin significantly reduces the risk of colorectal cancer (搜索) recurrence in patients with PI3K (搜索) mutations.
The ALASCCA trial demonstrated a 51% to 58% reduction in recurrence risk in patients with specific PI3K (搜索) pathway alterations.
The study highlights the potential for repurposing aspirin as a cost-effective adjuvant therapy and emphasizes the importance of genomic testing.
Aspirin is showing promise in preventing colorectal cancer (搜索) recurrence in patients with tumors harboring PI3K (搜索) mutations, according to results from the ALASCCA trial presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. The study found that a daily dose of 160 mg of aspirin reduced the risk of cancer recurrence by more than 50% in patients with PI3K-mutated colorectal cancer.
ALASCCA Trial Details
The ALASCCA trial screened 3,508 patients with early-stage colorectal cancer (搜索) across multiple centers in Sweden, Denmark, Finland, and Norway. Researchers identified 626 patients with somatic alterations in the PI3K (搜索) signaling pathway and randomly assigned them to receive either 160 mg of aspirin daily or a placebo for three years following surgery. The primary endpoint was time to colorectal cancer recurrence (TTR) in patients with PIK3CA exon 9/20 mutations. Secondary endpoints included disease-free survival (DFS) in the PIK3CA exon 9/20 group, TTR and DFS in patients with other PI3K mutations, and safety.
Significant Reduction in Recurrence Risk
The study revealed that patients taking daily aspirin had a 51% lower risk of cancer recurrence if they had a mutation in their PIK3CA mutation (HR, 0.49; 95% CI, 0.24-0.98; P = 0.044). Specifically, recurrence was observed in 7.7% of patients taking aspirin versus 14.1% of those on placebo. Similarly, patients with other PI3K (搜索) mutations experienced a 58% lower risk of cancer recurrence with aspirin (HR, 0.42; 95% CI, 0.21-0.83; P = 0.013), with recurrence rates of 7.7% and 16.8% in the aspirin and placebo groups, respectively.
Impact on Disease-Free Survival
While there was no statistically significant difference in 3-year disease-free survival (DFS) rates among those who received aspirin vs placebo in Group A (HR, 0.61; 95% CI, 0.34-1.08; P = .091), aspirin use significantly improved DFS rates in Group B (HR, 0.51; 95% CI 0.29-0.88; P = 0.17).
Safety Profile
Adverse events were more frequent in the aspirin group (301 vs 228), including severe adverse events (57 vs 38). However, researchers noted that the incidence of severe adverse events was rare and consistent with the known safety profile of aspirin. Severe adverse events included late post-operative complications, deep vein thrombosis, and embolism. Four patients in the aspirin group experienced hemorrhages, compared to none in the placebo group.
Expert Commentary
Dr. Anna Martling, lead researcher and professor of surgery at the Karolinska Institute (搜索) in Sweden, emphasized the potential of aspirin as a repurposed drug. "This is also an example of repurposing a safe, inexpensive, and globally available drug, and it stresses the importance of upfront genomic testing in colorectal cancer (搜索) patients," she stated.
Dr. Pamela Kunz, chief of GI medical oncology at the Yale School of Medicine, who was not involved in the study, commented on the practice-changing implications of the findings. "It's really clear that this is a practice-changing study. It checks all of the boxes. It's effective, it's low risk, it's inexpensive, and it's easy to administer," Kunz said.
The Role of Genomic Testing
The study underscores the importance of genomic testing to identify patients who are most likely to benefit from aspirin therapy. As Dr. Kunz noted, early upfront genomic profiling is a critical question that remains for clinical practice. While aspirin is an inexpensive intervention, the cost of genomic testing needs to be considered in the overall cost-benefit analysis.
Implications for Clinical Practice
The findings suggest that low-dose aspirin could be a valuable adjuvant treatment option for colorectal cancer (搜索) patients with PI3K (搜索) mutations. However, clinicians should carefully weigh the potential benefits and risks of aspirin therapy, particularly in light of the increased risk of bleeding. Further research is needed to determine the optimal dose and duration of aspirin therapy, as well as the long-term effects on cancer recurrence and survival.