A study involving more than 1,000 cancer patients has found that a low dose of aspirin halves the risk of colorectal tumors returning after surgery. This readily available and inexpensive treatment could change health outcomes for a significant number of cancer survivors who have problematic gene variants.
Researchers from Karolinska Institutet and Karolinska University Hospital screened 3,508 patients with stage I, II, or III rectal cancer or stage II or III colon cancer, finding that 1,103 of these people had a specific variant in the PI3K pathway – the genetic marker of interest. The team then conducted a double-blind, randomized, placebo-controlled trial on this gene-altered cohort, with 626 patients receiving 160-mg aspirin daily for three years and the remainder taking a placebo.
This study, known as the ALASCCA trial, was a massive effort involving 33 hospitals in Sweden, Norway, Denmark and Finland. The team prioritized people with the PIK3CA gene mutation, as well as people with other moderate or high impact variants in PIK3R1 and PTEN. The researchers selected for these genetic alterations because some previous research has shown that aspirin intervention has had a positive impact on suppressing tumor growth.
"Aspirin is being tested here in a completely new context as a precision medicine treatment," said first author Anna Martling, a professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet. "This is a clear example of how we can use genetic information to personalize treatment and at the same time save both resources and suffering."
What they found was that for people with the genetic mutation in PIK3, aspirin lowered the risk of recurrence by 55% compared with placebo treatment. The researchers believe that the benefit likely comes from aspirin acting in several ways – by reducing inflammation and inhibiting platelet function and tumor growth. Overall, aspirin makes the environment more challenging for cancer to get a foothold in, particularly for people with the genetic makeup predisposed to dysregulated cell function, where cancer cell growth and division is more likely.
"Although we do not yet fully understand all the molecular links, the findings strongly support the biological rationale and suggest that the treatment may be particularly effective in genetically defined subgroups of patients," said Martling. "Aspirin is a drug that is readily available globally and extremely inexpensive compared to many modern cancer drugs, which is very positive."
Earlier largely observational studies have also found that aspirin is associated with a meaningful drop in the recurrence of colorectal cancer, however clinical trial evidence has been inconclusive – until now. The added advantage of aspirin is, of course, that it's already a widely known and studied drug, making it a strong candidate for being clinically recommended for cancer survivors with certain genetic mutations. It's also being investigated in other settings including ovarian and gastrointestinal cancers.
Each year, around two million people worldwide are diagnosed with colorectal cancer – and approximately 15-20% of patients have activating mutations in the PI3K pathway, primarily in the PIK3CA gene.
"The estimated three-year cumulative incidence of recurrence was 7.7% with aspirin and 14.1% with placebo," noted the researchers. "Aspirin led to a significantly lower incidence of colorectal cancer recurrence than placebo among patients with PIK3CA hotspot mutations in exon 9 or 20 and appeared to have a similar benefit among those with other somatic alterations in PI3K pathway genes."
The study was published in The New England Journal of Medicine.
Source: Karolinska Institutet
