Women with ovarian cancer had significantly better survival if they were on statin therapy in addition to cancer-specific treatment, a review of registry-based data showed.
By multivariate analysis, statin use was associated with a 34% reduction in the survival hazard among 1,510 Medicare-age women (P<0.0001). Closer examination of the data showed that the survival benefit was limited to lipophilic statin agents and to use of moderate- and high-dose therapy, as reported here at the Society of Gynecologic Oncology meeting.
“These data confirm that stain use is associated with an improvement in overall survival [OS] in epithelial ovarian cancer patients who have undergone primary debulking surgery,” said Tilley Jenkins Vogel, MD, of Cedars-Sinai Medical Center in Los Angeles. “This effect was independent of other known prognostic factors such as age, stage, and comorbid medical conditions.
“This is the largest series in the literature to support an anticancer effect of statin therapy on epithelial ovarian cancer with a concomitant improvement in ovarian cancer survival. These data support the further study of statin use as a therapy in women with epithelial ovarian cancers.”
Numerous studies have provided evidence of various pleiotropic effects of statins, including a reduction in cancer risk and improved disease-specific survival among cancer patients, including patients with ovarian cancer. A retrospective review of 126 patients with advanced ovarian cancer showed improved survival among statin users. A retrospective cohort study of 442 patients with stages I-IV ovarian cancer showed a survival benefit only in patients with nonserous tumors.
Clinical and in vitro data have suggested differential effects by statin class, as the greatest benefit has been observed in association with use of lipophilic agents, said Vogel. Putative anticancer mechanisms of statins have included inhibition of cell division, reduced synthesis of mevalonate-acid pathway intermediates, promotion of apoptosis, and synergism with platinum chemotherapy.
Vogel and colleagues hypothesized that statin use improves outcomes in epithelial ovarian cancer by exerting favorable effects on tumor biology. To test the hypothesis they analyzed Medicare-linked data from the NCI Surveillance, Epidemiology, and End Results program for newly diagnosed epithelial ovarian cancer during 2007 to 2009.
Only patients who underwent surgical resection were included. Statin use was defined by an existing prescription at the time of surgery or a new prescription after surgery. The data showed that 636 of the 1,510 patients qualified as statin users during the study period. The statin of choice was a lipophilic agent in 88.7% of cases — atorvastatin (Lipitor), lovastatin (Mevacor), or simvastatin (Zocor). Dosage was moderate in 70.4% of statin users and high in 15.3%.
Statin users had a median OS of 32.2 months versus 28.7 months for non-users (P<0.001). Patients with stage III disease had a greater survival benefit with statin use (31.7 versus 25.9 months, P<0.001). The statin benefit applied to patients with serous (HR 0.69, 95% CI 0.55-0.87, P=0.002) and nonserous tumors (OR 0.33-0.82, P=0.005).
Consistent with previous studies, the data showed that lipophilic statins conferred a significant survival advantage (HR 0.63, 95% CI 0.52-0.77, P<0.0001), which was consistent across all three drugs in the class (HR 0.68 to HR 0.58, P=0.009 to P=0.002). Survival was not improved among patients taking hydrophilic statins as compared with statin non-users, Vogel reported.
Moderate-dose therapy was associated with a 40% reduction in the survival hazard (P<0.0001) and high-dose therapy with a 33% reduction (P=0.04). Patients on low-dose statin therapy had survival similar to that of nonusers.
Acknowledging limitations of the study, Vogel cited the retrospective nature of the analysis, reliance on coding to identify tumor histology, and lack of laboratory results to examine results in relation to cholesterol-lowering effects of the statins.
“These data should be validated in a prospective analysis of statin therapy in ovarian cancer patients,” she said. “Identification of biomarkers that predict response to statin therapy would help further select a patient population and guide treatment and should be investigated in both in vitro and in vivo settings.”
The presentation was included in a session about repurposing noncancer therapies in gynecologic cancers. Invited discussant Kala Visvanathan, MD, of Johns Hopkins’ Bloomberg School of Public Health, said studies such as the one reported by Vogel can be informative when clinical trials have not been conducted or are not possible.
However, the studies share common problems and shortcomings: lack of detailed clinical information, confounding by indication, generalizability of results, appropriate temporality for causal inference, and appropriate exposure risk window, among others.
“[Repurposing drugs] is a promising area both from the public and private sector,” said Visvanathan. “Well conducted observational studies are needed, as well as translation to clinical trials. Information on these drugs should be incorporated into new clinical trials for evaluation of drug interactions. More mechanistic studies are needed to identify targets.”
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