Results from the Adjuvant Low dose Aspirin in Colorectal Cancer (ALASCCA) clinical trial demonstrate a survival benefit associated with aspirin use in patients with non-metastatic colorectal cancer (CRC) harbouring phosphoinositide 3-kinase (PI3K) pathway alterations. Identification of patients in routine clinical care is required for implementation of this therapeutic approach. A real-world analysis of reflex diagnostic testing was performed to assess prevalence of PI3KCA and PTEN gene alterations and potential clinical impact. Next generation sequencing panel testing of all newly diagnosed CRC as part of a Lynch screening service began in the Northern Ireland Cancer Network in 2022.
Profiling, using a capture hybridisation assay and custom Small Cancer Panel covers all coding regions of PTEN and PIK3CA with a limit of detection of 4% variant allele frequency (VAF). 1516 CRC patients underwent genomic profiling at the point of diagnosis from January 2024-March 2025. Across all CRC stages, 170 patients (11.2%) had tumours harbouring PIK3CA mutations with the majority occurring in exon 9 and 20. A further 51 of 1516 tumours (3.4%) demonstrated PTEN mutations. Of 221 patients with PIK3CA/PTEN alterations, 174 (79%) had non-metastatic CRC, of whom 6 (3.4%) had an absolute contraindication to aspirin use. Overall, 168 (11.1%) of 1516 patients in this cohort were therefore identified by this reflex testing pathway as potentially eligible for treatment.
Prevalence of PIK3CA and PTEN alterations in this series (14.6%) was lower than in the ALASCCA trial (37%) but these results represent a real-world rather than a highly selected trial population. Regardless, our findings support implementing testing for use of a safe, inexpensive repurposed drug and underscore the importance of upfront testing for timely treatment decision-making and implementation of trial findings into routine practice.
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