Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial

Chia JWK 1 , Segelov E 2 , Deng Y 3 , Ho GF 4 , Wang W 5 , Han S 1 Show all authors , Sharma A 6 , Ding K 7 , Chen G 8 , Jeffery MG 9 , Tham CK 1 , Ahn JB 10 , Nott L 11 , Zielinski R 12 , Chao TY 13 , van Hagen T 14 , Wei PL 15 , Day F 16 , Mehta S 17 , Yau T 18 , Peng J 19 , Hayes TM 20 , Li Y 21 , Gandhi M 22 , Foo EMJ 1 , Rahman N 23 , Rothwell P 24 , Ali R 25 , Simes J 26 , Toh HC 27

Affiliations 

  • 1 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
  • 2 Department of Clinical Research and Department of Radiation Oncology, Faculty of Medicine, University of Bern, Bern, Switzerland; Australasian Gastro-Intestinal Trials Group (AGITG), GI Cancer Institute @Lifehouse, Camperdown, NSW, Australia
  • 3 Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  • 4 University Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia
  • 5 The First People's Hospital of Foshan, Foshan, China
  • 6 Department of Medical Oncology, AIIMS, New Delhi, India
  • 7 Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  • 8 Department of Colorectal Surgery, Sun Yat-sen University Cancer Centre, Guangzhou, China
  • 9 Australasian Gastro-Intestinal Trials Group (AGITG), GI Cancer Institute @Lifehouse, Camperdown, NSW, Australia; Oncology Service, Christchurch Hospital, Christchurch, New Zealand
  • 10 Division of Medical Oncology, Yonsei University College of Medicine, Seoul, South Korea
  • 11 Tasmanian Health Service, Royal Hobart Hospital, Hobart, TAS, Australia
  • 12 Central West Cancer Care Centre, Orange Base Hospital, Orange, NSW, Australia; Western Sydney University, Sydney, NSW, Australia
  • 13 Hematology & Oncology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
  • 14 St John of God Subiaco Hospital, Subiaco, WA, Australia
  • 15 Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
  • 16 Australasian Gastro-Intestinal Trials Group (AGITG), GI Cancer Institute @Lifehouse, Camperdown, NSW, Australia; Medical Oncology, Calvary Mater Newcastle and University of Newcastle, Newcastle, NSW, Australia
  • 17 Department of Digestive Diseases and Clinical Nutrition Member, Disease Management Group - Gastrointestinal Oncology, Tata Memorial Hospital, Mumbai, India
  • 18 Department of Medicine, Queen Mary Hospital and Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
  • 19 Department of Medical Oncology, Zhongshan City People's Hospital, Zhongshan, China
  • 20 South West Oncology, South West Regional Cancer Centre, Warrnambool, VIC, Australia
  • 21 Department of Gastrointestinal Surgery, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, China
  • 22 Department of Biostatistics, Singapore Clinical Research Institute, Singapore; Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore
  • 23 Department of Biostatistics, Singapore Clinical Research Institute, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
  • 24 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  • 25 MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK; Public Health Research Centre, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
  • 26 Australasian Gastro-Intestinal Trials Group (AGITG), GI Cancer Institute @Lifehouse, Camperdown, NSW, Australia; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  • 27 Division of Medical Oncology, National Cancer Centre Singapore, Singapore. Electronic address: toh.han.chong@singhealth.com.sg
Lancet Gastroenterol Hepatol, 2025 Mar;10(3):198-209.
PMID: 39824200 DOI: 10.1016/S2468-1253(24)00387-X

Abstract

BACKGROUND: Aspirin is a simple, globally available medication that has been shown to reduce the incidence of colorectal cancer. We aimed to evaluate the safety and efficacy of aspirin in the secondary prevention of colorectal cancer.

METHODS: This phase 3, randomised, double-blind, placebo-controlled trial was conducted at 66 centres across 11 countries and territories (ten in Asia-Pacific; one in the Middle East). The trial included patients aged 18 years and older with Dukes' C or high-risk Dukes' B colon cancer or Dukes' B or C rectal cancer who had undergone resection and had completed standard adjuvant therapy (at least 3 months of chemotherapy). Patients with contraindications to aspirin, familial syndromes of colorectal cancer, recent other cancers, and clinically significant history of cardiovascular disease or stroke were excluded. Patients were randomly assigned (1:1) to aspirin 200 mg daily or placebo for 3 years, and were followed up for 5 years. Randomisation was stratified by study centre, tumour site and stage, and inclusion of oxaliplatin in adjuvant chemotherapy. The patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was disease-free survival. The primary analysis used a stratified Cox model in those commencing study treatment (modified intention-to-treat population), analysing all events to March 31, 2023. Safety was analysed in the same population. This trial is registered at ClinicalTrials.gov (NCT00565708). The primary analysis has been completed, but translational studies of putative aspirin sensitivity biomarkers are ongoing.

FINDINGS: Between Feb 25, 2009, and June 30, 2021, 1587 patients underwent randomisation, of whom 1550 were included in the modified intention-to-treat analysis: 791 (51%) in the aspirin group and 759 (49%) in the placebo group. Of these patients, the median age was 57 years (IQR 48-65); 897 (58%) were male and 653 (42%) female; 271 (17%) had Dukes' B colon cancer, 770 (50%) Dukes' C colon cancer, and 509 (33%) rectal cancer. Median follow-up at data cutoff was 59·2 months (IQR 36·7-60·0). 5-year disease-free survival was 77·0% (95% CI 73·6-80·0) in the aspirin group and 74·8% (71·3-77·9) in the placebo group (hazard ratio of 0·91 [95% CI 0·73-1·13]; p=0·38). Any-grade adverse events were reported in 390 (49%) of 791 patients in the aspirin group versus 386 (51%) of 759 in the placebo group. Serious adverse events were reported in 95 (12%) patients in the aspirin group versus 107 (14%) in the placebo group. There were no treatment-related deaths in either group. Among adverse events of special interest, there were no cases of acute myocardial infarction in the aspirin group versus two in the placebo group; no ischaemic cerebrovascular events in the aspirin group versus two in the placebo group; and three major gastrointestinal bleeds in the aspirin group versus one in the placebo group.

INTERPRETATION: In patients with colorectal cancer, aspirin 200 mg daily for 3 years after completion of standard adjuvant therapy was well tolerated but did not significantly improve disease-free survival.

FUNDING: SingHealth Foundation, National Medical Research Council Singapore, National Cancer Centre Research Fund, Rising Tide Foundation, Lee Foundation, Lee Kim Tah Foundation, Duke-NUS Khoo Bridge Funding Award, Terry-Fox Run, Silent Foundation, Cancer Australia, Bowel Cancer Australia, and Cancer Council NSW.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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