Abstract 2333: Aspirin may extend biliary tract cancer survival: Results from population-based cohort

Abstract

Abstract Background: Biliary tract cancers (BTCs) are rare, but lethal cancers with a median survival of <12 months. Because of this poor prognosis, there is a critical need for treatments that extend survival. Cyclooxygenase-2 (COX-2) is an enzyme responsible for producing prostaglandin E (PGE). PGEs increase mucin production and reduce bile flow in the gallbladder, leading to gallstones, a precursor to gallbladder cancer. Overexpression of COX-2 due to chronic inflammation from cholangiocarcinoma has been found to enhance PGE production and promote tumor growth. Previous research suggests that COX-2 inhibitors, such as aspirin, may slow cancer cell growth. We investigated aspirin use following diagnosis and overall survival in a large cohort of patients with BTCs. Methods: All patients diagnosed with incident biliary tract cancer between 1990 to 2017 were selected from the population-based United Kingdom’s Clinical Practice Research Datalink. Site-specific associations between aspirin use after BTC diagnosis and overall survival was analyzed using Cox proportional hazards models with aspirin use modeled as time-dependent, adjusting for age at diagnosis, sex, comorbidities, history of aspirin use, and use of statins, using follow-up time as the time scale. Results: We identified 3,211 biliary tract cancer cases in which 2,694 (84%) deaths occurred after an overall median follow-up time of 5 months. The table presents the number of cases by cancer subtype, deaths, and median survival time. Aspirin use following a diagnosis of BTC was associated with a reduction in mortality for each of the BTC sites: gallbladder, HR 0.41 (95% CI: 0.28, 0.61); cholangiocarcinoma, HR 0.46 (95% CI: 0.36, 0.60); ampulla of Vater, HR 0.24 (95% CI: 0.11, 0.51); and mixed, HR: 0.51 (95% CI: 0.33, 0.78). Conclusions: The use of aspirin after BTC diagnosis was associated with a lower risk of overall mortality. These results warrant additional studies to understand the mechanisms underlying improved survival with aspirin use. Table.Association between post-BTC diagnosis aspirin use versus no use and survival in the UK CPRD datasetCancer siteBTC patients N (%)Mortality N (%)Median survival time in months (interquartile range)HR (95% CI)*Gallbladder668 (23)555 (83)3.9 (2 - 11)0.41 (0.28, 0.61)Cholangiocarcinoma1,560 (53)1321 (85)4.8 (2 - 12)0.46 (0.36, 0.60)Ampulla of Vater224 (8)142 (63)9 (4 - 21)0.24 (0.11, 0.51)Mixed484 (16)401 (83)5 (2 - 13)0.51 (0.33, 0.78)*Adjusted for age at diagnosis, comorbidities, prior aspirin use, and use of statins.Abbreviations: CPRD, Clinical Practice Research Datalink; CI, confidence interval; HR, hazard ratio; N, number; and UK, United Kingdom. Citation Format: Sarah S. Jackson, Bin Zhu, Ruth Pfeiffer, Zhiwei Liu, Shahinaz Gadalla, Jill Koshiol. Aspirin may extend biliary tract cancer survival: Results from population-based cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2333.