LBA29 - Aspirin after standard adjuvant therapy for colorectal cancers (ASCOLT): An international, phase III, randomised, placebo-controlled trial

Background

Aspirin is an inexpensive, readily available treatment globally with the potential to be an effective adjuvant therapy to prevent recurrence of colorectal cancer (CRC) after completing standard primary treatment. This landmark study conducted entirely in the Asia-Pacific region, where incidence of CRC is increasing, is the first international Phase III double-blind placebo-controlled trial to report the activity of aspirin in the secondary prevention of CRC (NCT 00565708).

Methods

Patients with Dukes’ C and high-risk Dukes’ B CRC were randomised to Aspirin 200mg daily or placebo for 3 years after surgery and completion of standard adjuvant therapy (including 3+ months of chemotherapy) and followed for 5+ years. The primary endpoint was Disease-Free Survival (DFS). The primary analysis used a stratified Cox model, with those commencing study treatment (modified intention to treat (mITT) and with all events up to 31/03/2023. Secondary endpoints included overall survival (OS) and DFS in the colon cancer group. Translational biomarker studies are ongoing.

Results

Between 25/02/2009 and 31/03/2021, 1587 participants were randomised from 66 centres across 10 Asia-Pacific countries and 1550 were included in the mITT analysis: 791 on aspirin and 759 placebo. Of these, 897 were males; 271 Dukes’ B colon cancers, 769 Dukes’ C colon cancers and 510 rectal cancers. Estimated DFS at 5 years was 77% (95% CI 74-80%) and 75% (95% CI 71-78%) for aspirin and placebo respectively with an estimated hazard ratio (HR) of 0.91 (95% CI 0.73-1.13, p=0.38). Overall survival showed HR favouring aspirin of 0.75 (95% CI 0.53-1.07, p=0.11). In the colon cancer group, the HR for DFS was 0.86 (95% CI 0.66 - 1.13, p=0.28). Adverse events were low in both arms and aspirin was well tolerated.

Conclusions

Our study did not show a significant DFS or OS benefit of aspirin therapy as an additional adjuvant therapy for patients with colorectal cancer. Nevertheless, results are still consistent with a more moderate, yet still worthwhile benefit for the global populations, and results from ongoing studies are awaited. Analysis of special subpopulations predicted to benefit from aspirin in ASCOLT and other trials, may also be critical.

Clinical trial identification

NCT00565708.

Editorial acknowledgement

NIL / Not applicable

Legal entity responsible for the study

National Cancer Centre Singapore.

Funding

National Medical Research Council, Singapore National Cancer Cancer Singapore Research Fund SinghealthFoundation, Singapore National Health and Medical Research Council, Australia Lee Foundation, Singapore Lee Kim TahFoundation, Singapore SilentFoundation, Singapore Rising Tide Foundation, Switzerland Bayer AG (Study Drug only).

Disclosure

All authors have declared no conflicts of interest.