Abstract 164: PIK3CA mutation, aspirin use and mortality in patients with metastatic colorectal cancer participating in early-phase clinical trials .

Abstract

Abstract Background: Regular use of aspirin use has been associated with reduced risk of colorectal cancer (CRC) and CRC-specific mortality. Preclinical data demonstrates that aspirin down-regulates phosphatidylinositol 3-kinase (PI3K) signaling activity by inhibiting cyclooxygenase-2. Recently, regular use of aspirin was found to be associated with better survival among patients with mutated, but not wild-type PIK3CA CRC. Methods: 296 patients with CRC referred to the Clinical Center for Targeted Therapy (CCTT) at the MD Anderson Cancer Center from 10/2008 were analyzed for PIK3CA mutation status. Survival and medication data was collected from 243 patients who participated in early-phase clinical trials. Aspirin use was defined as regular aspirin use at the time of the initial CCTT clinic visit. Primary outcome was time from the initial CCTT visit till the last day of follow up or death. Cox proportional-hazards model was used to compute the multivariate hazard ratio (HR) for mortality. Results: Mean age of the study cohort was 58 years (standard deviation, 11 years). 55% was male and 72% were Caucasian, 15%, Afro-American, and 10%, Hispanic. Median survival was 8.8 months. PIK3CA mutation was found in 38 patients (15.6%), and 25 (10.3%) of them were using aspirin. Aspirin users and nonusers were similar in clinical characteristics except for older age in aspirin users (mean difference of 8.6 years, p<0.001). There was no difference in PIK3CA mutation status between aspirin users and nonusers (14.6% vs. 16.5%, p=0.79). Prognostic impact of the Royal Marsden Hospital (RMH) score (albumin <3.5 vs. ≥3.5 g/dL, lactate dehydrogenase (LDH) > upper limit of normal (ULN) vs. ≤ULN, and >2 vs. ≤2 sites of metastases) was ascertained in our cohort. Aspirin use was not associated with difference in survival (HR=1.37, 95% confidence interval [CI]=0.80-2.35, p=0.25). This was also true with adjustment for the RMH score (adjusted HR [AHR]=1.56, 95%CI=0.91-2.67, p=0.11). Among patients with wild-type PIK3CA CRC, aspirin use was associated with inferior survival (AHR=1.80, 95%CI=1.01-3.23, p=0.04). In contrast, among patients with mutated PIK3CA, aspirin use did not impact survival (AHR=0.75, 95% CI=0.17 to 3.20, P=0.70) Conclusion: Aspirin use was associated with shorter survival in patients with wild-type PIK3CA metastatic CRC treated with early-phase clinical trials, but not in patients with mutated PIK3CA. Larger studies are required to further explore and validate possible interactive effect between PIK3CA mutation and aspirin use on survival of patients with metastatic CRC. Citation Format: Young Kwang Chae, Kunwha Kim, David S. Hong, Gerald S. Falchook, Sarina A. Piha-Paul, Jennifer J. Wheler, Aung Naing, Siqing Fu, Apostolia M. Tsimberidou, Raph G. Zinner, Vivek Subbiah, Vanda M. Stepanek, Robert A. Wolff, Razelle Kurzrock, Filip Janku. PIK3CA mutation, aspirin use and mortality in patients with metastatic colorectal cancer participating in early-phase clinical trials . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 164. doi:10.1158/1538-7445.AM2013-164