Evidence map›Paper›PMID 42475879›Full record

SynthesisEBioMedicine2026

Adjuvant aspirin for colorectal cancer with PIK3CA-mutated and COX-2 overexpressed tumours: the ASCOLT translational research study and meta-analysis.

Eva Segelov, Shan Li, Isabel Li, Dmitri Mouradov, Sonia Yip, Daphne Day, Mark Jeffery, Rob Zielinski, Louise Nott, Yuntian Sun and 10 more

Registry-linked trialAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00565708 (Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers - An International, Multi-Center, Double Blind, Randomized Placebo Controlled Phase III Trial), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00565708 phase3unknown statusnot on this map

Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers - An International, Multi-Center, Double Blind, Randomized Placebo Controlled Phase III Trial

TypeinterventionalSponsorNational Cancer Centre, SingaporeRan2008 to 2024Enrolled1,587ConditionsColorectal CancerArmsplacebo, Acetylsalicylic acid
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Eva SegelovDepartment of Clinical Research, Faculty of Medicine and Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Shan LiPersonalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Isabel LiNHMRC Clinical Trials Centre, University of Sydney, NSW, Australia.
Dmitri MouradovPersonalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Sonia YipNHMRC Clinical Trials Centre, University of Sydney, NSW, Australia.
Daphne DayDepartment of Oncology, Monash Health and Monash University, Victoria, Australia.
Mark JefferyOncology Department, Christchurch Hospital, New Zealand.
Rob ZielinskiMedical Oncology Department, Orange Health Service, Orange, NSW, Australia.
Louise NottRoyal Hobart Hospital, Hobart, Tasmania, Australia.
Yuntian SunDepartment of Pathology, National Cancer Center, Chinese Academy of Medical Sciences, Beijing, China.
Michael ChristieDepartment of Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Gwo Fuang HoClinical Oncology Department, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Tsu-Yi ChaoHematology/oncology Department, Shuang Ho Hospital, New Taipei City, Taiwan.
Nabilah RahmanBiostatistics, Singapore Clinical Research Institute, Consortium for Clinical Research and Innovation Singapore, Singapore.
Estelle FooDivision of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
John ChiaMedical Oncology, Curie Oncology, 329563, Singapore, Singapore.
Val GebskiNHMRC Clinical Trials Centre, University of Sydney, NSW, Australia.
Han Chong TohDivision of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
Oliver M SieberPersonalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: sieber.o@wehi.edu.au.
John SimesNHMRC Clinical Trials Centre, University of Sydney, NSW, Australia. Electronic address: john.simes@sydney.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundASCOLT compared adjuvant aspirin versus (vs) placebo in 1587 patients with colorectal cancer (CRC) and reported no significant improvement in disease-free survival (DFS). Subsequently, two randomised controlled trials (RCTs) reported benefit of adjuvant aspirin in CRC patients with somatic PI3K-related mutations.

methodsThe ASCOLT Translational Research (TR) study was a preplanned subgroup analysis by PIK3CA mutation status and COX-2 overexpression, and an exploratory analysis including PTEN mutation status. Among 778 participants who commenced study medication, tissue was evaluable for targeted next generation sequencing of PIK3CA and PTEN in 289 tumours and by Sanger sequencing for PIK3CA exon 9 or 20 (9/20) mutations in a further 108. PTGS2/COX-2 expression was assessed by immunohistochemistry in 450. Hazard ratio (HR) and 95% confidence intervals (CI) for DFS of aspirin vs placebo in subgroups were assessed in Cox models. A systematic review of completed RCTs of adjuvant aspirin in CRC patients with PIK3CA mutations was also undertaken. REGISTRATION: NCT00565708 and ACTRN12614000513617.

findingsAmong 397 patients with tumour assessable for PIK3CA, there were 80 recurrences, 40 deaths and 86 DFS events after 5 years follow-up. Among 69 (17%) with PIK3CA mutations (any exon), there were 8 vs 8 DFS events on placebo vs aspirin (HR 0.93 (95% CI 0.35-2.47); in 45 (11%) with exon 9/20 mutations, 7 vs 4 events (HR 0.72 (95% CI 0.21-2.46) and in 84 (21%) with PIK3CA or PTEN mutations, 8 vs 9 events (HR 1.23 (95% CI 0.47-3.19). Tumours were positive for COX-2 overexpression in 307 (69%) with 28 vs 34 events (HR 0.99 (95% CI 0.60-1.63). A meta-analysis of trials in patients with PIK3CA exon 9/20 mutations showed reduced DFS events with HR 0.61 (95% CI 0.39-0.96).

interpretationIn ASCOLT TR, adjuvant aspirin was not associated with significantly improved DFS in CRC with PI3K-related mutations or COX-2 overexpression, albeit with wide confidence intervals. Combined results of the three published trials showed improved DFS among patients with PIK3CA exon 9/20 mutations. Moderate, but important, effects of aspirin in other patient groups have not been excluded.

fundingNational Health and Medical Research Council, Australia; Cancer Australia; National Cancer Centre Singapore Cancer Fund; Rising Tide Foundation; SingHealth Duke-NUS Academic Clinical Programme; Lee Foundation; Lee Kim Tah Foundation; Silent Foundation; Australasian Gastro-Intestinal Trials Group.

Indexed as

AspirinClass I Phosphatidylinositol 3-KinasesColorectal NeoplasmsCyclooxygenase 2MutationAgedChemotherapy, AdjuvantFemaleHumansMaleMiddle AgedTranslational Research, BiomedicalTreatment OutcomeAspirinClass I Phosphatidylinositol 3-KinasesCyclooxygenase 2PIK3CA protein, humanAdjuvant treatmentAspirinColorectal cancerCOX-2 overexpressionPIK3CA mutationRandomised

Identifiers

PMID42475879
PMCPMC13393707

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.