Abstract OT2-4-01: Add-aspirin trial: A phase III double-blind placebo-controlled randomized trial assessing the addition of aspirin after standard primary therapy in breast cancer and other early stage common solid tumours (CRUK/12/033)

Abstract

Abstract Background: There is a significant body of in vitro evidence and pre-clinical data which demonstrates that aspirin inhibits the growth of tumours and prevents the development of metastases[1]. A recent meta-analysis using individual patient data from randomized trials evaluating the cardiovascular effects of aspirin reports a reduction in cancer deaths after 5 years (hazard ratio 0.46, 95% confidence interval 0.27-0.77)[2]. Effects on risk of metastases and death following a cancer diagnosis have also been observed[3]. An analysis of the Nurses’ Health Study found that aspirin use following a diagnosis of stage I-III breast cancer was associated with a lower risk of breast cancer death (for those taking aspirin 2-5 times per week, relative risk 0.27, 95% confidence interval 0.15-0.47)[4]. Concerns over toxicity have limited the use of aspirin as a primary prevention agent against cancer. In the adjuvant setting the benefit:risk ratio will be different with higher morbidity and mortality from recurrent cancer potentially outweighing the risks associated with regular aspirin use. The Add-Aspirin trials will investigate whether regular aspirin use after curative treatment for localised malignancy can prevent tumour recurrence and prolong survival. As an inexpensive drug with a potential therapeutic role in several common cancers, aspirin could have a huge impact on the global cancer burden. Trial design: Multicentre, international, phase III, double-blind, placebo-controlled randomized trial in patients with early breast cancer. Participants will be randomised to enteric-coated aspirin 100mg, aspirin 300mg or matching placebo daily for at least 5 years. Parallel trials based on a common infrastructure will be conducted in colorectal, gastro-oesophageal and prostate cancer. Eligibility criteria: Patients who have undergone primary therapy, including curative surgery and appropriate neoadjuvant/adjuvant therapies for histologically confirmed invasive breast cancer which is node positive or node negative with high-risk features. Patients who have already participated in other primary treatment trials may be eligible subject to agreement from the trial management groups. Specific aims: The primary outcome will be disease-free survival. Secondary endpoints include overall survival, toxicity, cardiac morbidity and assessment of overall healthcare benefits. Translational work will investigate mechanisms of action and biomarkers for toxicity and treatment efficacy (including PIK3CA mutation status and COX-2 expression). Statistical methods: Approximately 3100 patients will be needed to test for a 4% improvement in DFS associated with aspirin use. [1] Langley RE et al. Br J Cancer. 2011;105(8):1107-13. [2] Rothwell PM et al. Lancet. 2011;377(9759):31-41. [3] Rothwell PM et al. Lancet. 2012;379(9826):1591-601. [4] Holmes MD et al. J Clin Oncol 2010;28(9):1467-72. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-4-01.