Lipophilic statin use was associated with a reduced risk of dying of epithelial ovarian cancer in a large observational study. Compared with never users, women with epithelial ovarian cancer who were taking any type of statins had a reduced mortality of 40%, and those taking lipophilic statins had a 43% reduction in mortality. Mortality reductions with statin use were observed across all subtypes of epithelial ovarian cancer. These findings were presented at a press briefing in advance of the 2020 American Association for Cancer Research (AACR) Virtual Meeting II and also during the meeting as a poster session.¹

“Reductions in mortality [with lipophilic statins] were observed across all stages, treatments, and epithelial ovarian cancer subtypes.”

— Kala Visvanathan, MD, MS

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“Among women with epithelial ovarian cancer, statin users have a significant reduction in ovarian cancer–specific mortality, particularly with lipophilic statins, compared with never users,” stated lead author Kala Visvanathan, MD, MS, of Johns Hopkins Bloomberg School of Public Health and Sidney Kimmel Cancer Center, Baltimore. “The reduction was observed in statin users just prior to and after diagnosis. A range of reductions in mortality were observed across all stages, treatments, and epithelial ovarian cancer subtypes. These findings warrant further evaluation of lipophilic statins in a randomized control trial and reinforce the value of examining existing therapies that are commonly used and inexpensive to reduce the global cancer burden.”

Despite advances in therapy, 5-year overall survival for women with epithelial ovarian cancer is below 50%, and there are no proven screening strategies yet to identify earlier-stage disease. “Most women present with advanced-stage disease, when surgery is not an option. There is a strong need for more effective treatments,” Dr. Visvanathan stated.

Statins are widely used in the United States to lower cholesterol. Statins are known to inhibit the first step in the mevalonate pathway (HMG-CoA reductase) and, in turn, downstream products that have been implicated in tumorigenesis. There are three different types: lipophilic, hydrophilic, or both.

“It is likely that more than one biologic mechanism contributes to the benefit seen in this study. Preclinical data suggest that multiple mechanisms may be involved. More basic science research is needed to identify specific patient subgroups. Lipophilic statins have demonstrated prominent immunologic effects and may impact immunosurveillance,” Dr. Visvanathan noted. Previous observational studies of statins and ovarian cancer mortality have had mixed results and have not had the sample size to evaluate as many statin types or tumor subtypes, she added.

Study Details

The large observational study included 10,062 women aged 18 and older diagnosed with incident ovarian cancer between 1995 and 2015. The women were part of the Finnish National Cancer Registry and the National Prescription Claims Database. The analysis was adjusted for several factors, including age at diagnosis; stage; epithelial ovarian cancer subtype; initial treatment; year of diagnosis; and concurrent receipt of beta-blockers and cardiac, diabetes, and nonstatin cholesterol-lowering medications. Women were followed from diagnosis to death or censoring. Patients were characterized as statin users or never users.

Among the 10,062 women, 2,621 were statin users; of these patients, 80% used lipophilic statins. The median duration of statin use was 7.5 years, and the median age at diagnosis was 67 among patients who ever used statins. The most common subtype of epithelial ovarian cancer in users and nonusers was serous carcinoma, the most aggressive subtype.

Statin use of any kind was associated with a 40% (95% confidence interval = 34%-46%) reduction in ovarian cancer–specific mortality vs no statin use. At 5 years, the reduction in mortality observed with statin use was 37%.

The use of lipophilic statins improved survival across all epithelial ovarian cancer subtypes by 40% in high-grade serous epithelial ovarian cancer, by 50% in endometrioid, by 70% in mucinous, and by 73% in borderline disease.

The type of care and the type of statin also made a difference in the magnitude of benefit of statin use. The benefit of statin use was greater in women treated with curative intent vs palliative intent (53% vs 45% reduction in mortality). Lipophilic statinswere associated with a 43% reduction in mortality. Reductions were also observed among those who used primarily simvastatin or atorvastatin. 

DISCLOSURE: Dr. Visvanathan reported no conflicts of interest.

REFERENCE

1. Visvanathan K, Modur S, Artama M, et al: Lipophilic statins show promise for treatment of epithelial ovarian cancer. 2020 AACR Virtual Annual Meeting II. Abstract 5782.