Aspirin may improve survival in PIK3CA-mutated colon cancer

Adjuvant treatment with aspirin appears to provide some protection in patients with resected, PIK3CA-mutant stage II and III colon cancer, demonstrating a clinically significant improvement (43 percent) in disease-free survival (DFS), suggests a study presented at ESMO Congress 2024.

This is the “first prospective, randomized trial to provide clinical evidence of a protective effect of adjuvant aspirin in patients with resected, PIK3CA-mutant stage II and III colon cancer,” said lead study author Dr Ulrich Güller from the Oncology Department, Spital STS AG Onkologiezentrum Thun-Berner Oberland, Switzerland.

The phase III, prospective-randomized placebo-controlled multicentre SAKK 41/13 trial sought to demonstrate the benefit of adjuvant aspirin treatment in PIK3CA-mutated colon cancer patients. Unfortunately, the SAKK 41/13 trial was closed prematurely due to financial constraints.

Initially, Güller and his team identified stage II and III colon cancer patients with a centrally assessed activating PIK3CA mutation in Exon 9 or 20. Those on aspirin or cyclo-oxygenase-2 (COX-2) inhibitors, with upper gastrointestinal bleeding within 12 months, multiple colonic malignancies, or rectal cancer were excluded from the study.

Güller and colleagues then randomized eligible participants in a 2:1 ratio to receive either aspirin 100 mg daily or placebo for 3 years. DFS was the primary outcome, while recurrence-free survival, overall survival, and adverse events were secondary.

DFS improvement

A total of 1,040 patients underwent screening for PIK3CA mutations, of whom 112 (median age 66 years, 42.9 percent female) met the eligibility criteria (74 in the aspirin arm and 38 in the placebo arm). Baseline characteristics were well-balanced between the treatment groups.

Nineteen DFS events occurred over a median follow-up of 4 years, with a hazard ratio (HR) of 0.57 (90 percent confidence interval [CI], 0.27‒1.22) in favour of aspirin (p=0.11). DFS rates at 3 years were 88.3 percent (90 percent CI, 80.1‒93.3) with aspirin and 82.4 percent (90 percent CI, 68.3‒90.7) with placebo. [ESMO 2024, abstract 512O]

At 5 years, the DFS rates were 86.5 percent (90 percent CI, 77.7‒92.0) with aspirin and 72.9 percent (90 percent CI, 55.7‒84.3) with placebo, with an absolute difference of 13.6 percent. Additionally, the HR for recurrence-free survival was 0.49 (90 percent CI, 0.21‒1.19; p=0.089), while that for overall survival was 0.71 (90 percent CI, 0.23‒2.13; p=0.3).

Notably, aspirin demonstrated a “very favourable” side effect profile, with none of those treated with aspirin experiencing severe adverse events.

“Even though these results are not statistically significant due to premature study closure, adjuvant aspirin warrants individual consideration in patients with resected, PIK3CA-mutant stage II/III colon cancer,” Güller said.

Aspirin works by inhibiting COX-2, which stimulates the production of prostaglandin2 (PGE2). PGE2 is responsible for increasing angiogenesis or the proliferation of tumour cells via PIK3CA ‒ AKT – mTOR pathway. PIK3CA is the downstream target of COX-2/PGE2, according to Güller and colleagues.