Regular aspirin (ASA) use and survival in patients with PIK3CA-mutated metastatic colorectal cancer (CRC).

Abstract

386 Background: Recent data has demonstrated that regular ASA use improves overall and cancer-specific survival in the subset of CRC patients harboring PIK3CA mutations. However, as this series only analyzed 15 PIK3CA mutant CRC patients with metastatic disease at diagnosis, it remains uncertain whether the survival benefit associated with regular ASA use extends to patients with metastatic disease. We combined data from two large academic institutions to explore the association between regular ASA use and survival in metastatic CRC. Methods: Patients with PIK3CA mutated CRC were identified at Moffitt Cancer Center (MCC) in Tampa, FL and Royal Melbourne Hospital (RMH) in Australia. Prospective clinicopathological data (including age, sex, site of disease) and survival data were available. At MCC, PIK3CA mutations were identified by exome sequencing using an Illumina Next Generation Sequencing platform with 50-100X coverage. At RMH, Sanger sequencing was used to identify PIK3CA mutations. Survival analyses were conducted using Cox regression. Results: We identified 187 CRC patients who harbored a PIK3CA mutation. Median age was 72 years and median follow up was 48 months. 49 (26%) patients used ASA regularly. 47 (25%) patients had metastatic disease at diagnosis. In univariate analyses, regular ASA use was not associated with improved overall survival (HR 0.87, p = 0.60), although there was a trend towards improved cancer-specific survival (HR 0.48, p = 0.06). In patients with stage-II or stage-III disease, regular ASA use did not improve overall, cancer-specific or recurrence-free survival. However, in stage-IV patients, regular ASA use was significantly associated with improved overall (HR 0.35, p = 0.04) and cancer-specific (HR 0.28, p = 0.02) survival in a univariate analysis. Conclusions: Our study demonstrates that in patients with metastatic CRC harboring a PIK3CA mutation, regular ASA use is associated with a significant overall and cancer-specific survival advantage. However, we were not able to confirm the survival advantage across all stages. To our knowledge, our study is the largest to examine ASA use in PIK3CA mutated CRC.