Impact of regular aspirin use on overall and cancer-specific survival in patients with colorectal cancer harboring a PIK3CA mutation

Abstract

Background Recent data have suggested that regular aspirin use improves overall and cancer-specific survival in the subset of colorectal cancer (CRC) patients harboring PIK3CA mutations. However, the number of PIK3CA-mutated CRC patients examined in these studies was modest. Our collaborative study aims to validate the association between regular aspirin use and survival in patients with PIK3CA-mutated CRC. Patients and methods Patients with PIK3CA-mutated CRC were identified at Moffitt Cancer Center (MCC) in the United States and Royal Melbourne Hospital (RMH) in Australia. Prospective clinicopathological data and survival data were available. At MCC, PIK3CA mutations were identified by targeted exome sequencing using the Illumina GAIIx Next Generation Sequencing platform. At RMH, Sanger sequencing was utilized. Multivariate survival analyses were conducted using Cox logistic regression. Results From a cohort of 1487 CRC patients, 185 patients harbored a PIK3CA mutation. Median age of patients with PIK3CA-mutated tumors was 72 years (range: 34 – 92) and median follow up was 54 months. Forty-nine (26%) patients used aspirin regularly. Regular aspirin use was not associated with improved overall survival (multivariate HR 0.96, p = 0.86). There was a trend towards improved cancer-specific survival (multivariate HR 0.60, p = 0.14), but this was not significant. Conclusions Despite examining a large number of patients, we did not confirm that regular aspirin use was associated with statistically significant improvements in survival in PIK3CA-mutated CRC patients. Prospective evaluation of this relationship is warranted.

Evaluation of Caspase 9 Activity Level in Hela Cell Line Exposed to Cytotoxic Dose of Aspirin

“…In line with our finding recent data have suggested that regular aspirin use improves overall and cancer-specific survival in the subset of colorectal cancer (CRC) patients [7]. Aspirin is also a promising chemopreventive agent and exerts significant therapeutic potentials in pancreatic cancer [8].…”

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology

“…Domingo et al 81 and Liao et al 82 found a survival advantage for posttreatment aspirin users only in patients whose tumors exhibit PIK3CA mutations; however, a recent cohort study did not validate these observations. 83 Multiple prospective studies are under way to address the potential benefit of adding aspirin or other nonsteroidal anti-inflammatory drugs to adjuvant therapy. This recommendation is supported by two systematic reviews 33,40 obtained from our systematic review.…”

Personalized Medicine—Current and Emerging Predictive and Prognostic Biomarkers in Colorectal Cancer

“…This is highlighted in a study by Kothari and colleagues, who combined data from two large academic institutions and examined the association between regular aspirin use and improved survival in PIK3CA-mutated CRC patients. The authors found that regular aspirin use was not associated with improved OS (multivariate HR 0.96; p = 0.86) and despite a trend towards improved cancer-specific survival (multivariate HR 0.60; p = 0.14), this was not significant [179]. As a result, mutations in PIK3CA may serve as a predictive biomarker for adjuvant aspirin therapy, however, further investigations involving prospective randomized studies are warranted.…”

“…In their prospective two cohort studies, coexistence of PIK3CA exon 9 and 20 mutations but not in either exon alone, was associated with significantly worse cancer-specific survival (log-rank p = 0.0008; multivariate HR = 3.51; 95% CI, 1.28-9.62] and OS (log-rank p = 0.0008; multivariate HR = 2.68; 95% CI, 1.24-5.77) [80] (Table 2). On the contrary, other studies suggest that mutant PIK3CA may not be as predictive as first thought [179]. This is highlighted in a study by Kothari and colleagues, who combined data from two large academic institutions and examined the association between regular aspirin use and improved survival in PIK3CA-mutated CRC patients.…”