Abstract 5782: Lipophilic Statins show promise for treatment of epithelial ovarian cancer

Abstract

Abstract Background: Repurposing statins for the treatment of ovarian cancer isappealing due to promising preclinical and epidemiologic data, broad access,low cost, and modest toxicity. To inform the design of a randomized clinicaltrial, we conducted a large observational study to identify subgroups ofovarian cancer (OC) patients that could benefit from statin treatment. Methods: Data from the Finnish national cancer registry waslinked to prescription claims on 10,062 women diagnosed with OC between 1995and 2015. A series of analyses were then conducted in OC patients to examinethe association between pre- and post-diagnostic statin use and mortality(cause-specific and all cause). Descriptive statistics were used tocharacterize patients at baseline. To address potential confounding due toindication for statin initiation we used time updated marginal structural Coxregression models with inverse probability of treatment weights to calculatehazard ratios (HR) and 95% confidence intervals (95% CIs) between users and neverusers. Analyses were adjusted for age at diagnosis, stage, OC subtype,treatments, year of diagnosis, and chronic disease medications. Results: The median (IQR) age of diagnosis among patients was 63(53-74) years, and median (IQR) follow up time was 4 (1.5-9.3) years. A totalof 2,621 patients were statin users of which 80% took statins classified aslipophilic. Median (IQR) duration of statin use was 7.5 (3.6-11.4) years.Eighty two percent of statin users filled 90% of their prescriptions. In timeupdated models, ever use of statins was associated with a 40% reduction in OCmortality compared to never use (HR Overall = 0.60(0.57-0.63).; HR Lipophilic = 0.78 (0.64-0.83).The benefit from statin use was greater in those being treated with curativeintent (HR=0.19; 0.18-0.20) rather than palliative intent (HR =0.41; 0.39-0.4).Further, reductions in OC mortality were also observed in women who primarilytook one specific lipophilic statin: HR Atorvastatin= 0.35;(0.22-0.50) and HR Simvastatin= 0.25;(0.22-0.34). Among women taking lipophilic statins, agreater reduction in mortality was observed with increasing statin dose (ptrend = 0.06). Lipophilic statin use was also associated with a reduction in OCmortality among most OC subtypes, but the magnitude of reduction varied: HighGrade Serous Carcinoma (HR= 0.43; 0.33-0.76); Endometroid (HR =0.65;0.34-0.78); Clear cell (HR= 1.02; 0.98-1.98); Mucinous (HR=0.60; 0.45-0.95);and Borderline (HR =0.30; 0.25-0.87). A reduction in OC mortality was alsoobserved in analyses limited to women who initiated lipophilic statinspost-diagnosis. Conclusion: Our results provide further evidence in support of theevaluation of lipophilic statins, particularly atorvastatin and/or simvastatin,for the treatment of OC in a randomized clinical trial. Citation Format: Kala Visvanathan, Shari Modur, Miia Artama, Teemu Murtola. Lipophilic Statins show promise for treatment of epithelial ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5782.