Lipophilic statin use is associated with reduced mortality risk in women with ovarian cancer, findings from a large observational study suggest.

The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.

When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).

Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.

Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.

Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.

Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.

Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.

Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.

Implications and next steps

The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.

“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.

“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”

Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”

The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).

Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.

“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.

“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”

The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.

SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.