Common medications and survival in women with ovarian cancer: A systematic review and meta-analysis

Objectives. Ovarian cancer is usually diagnosed at an advanced stage when five-year relative survival is <50%. Therefore, strategies to improve survival are required. Studies suggest associations between common chronic disease medications such as metformin, statins, beta-blockers, aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) and improved cancer survival. We aimed to review the evidence for a possible relation between these medications and survival among women with ovarian cancer. Methods. Weconducted four systematic reviews and evaluated the risk of bias in the included studies. Where possible, we calculated pooled hazard ratios (pHR) and 95% confidence intervals (CI), excluding studies considered to have the potential for immortal time bias (ITB) which, in practice, was the major source of bias. Results. We identified 36 studies evaluating one or more of the medications (metformin n= 8, statins n= 12, beta-blockers n= 11, aspirin and/or NA-NSAIDs n= 9). Werated 21 studies as ITB-free. The meta-analysis of the ITB-free studies suggested improved survival in statin users compared to non-users (pHR: 0.76, 95%CI: 0.68-0.85), but no overall survival benefit associated with use of metformin, beta-blockers, aspirin or NA-NSAIDs. The pooled result of two studies did, however, suggest a possible association between perioperative beta-blocker use and improved survival. Studies considered to have potential ITB were more likely to report survival benefits associated with these medications. Conclusion. Statin use is associated with better ovarian cancer survival but further study, preferably a clinical trial, is required. There are insufficient data to draw conclusions regarding metformin, beta-blockers, aspirin and NA-NSAIDs. (C) 2020 Elsevier Inc. All rights reserved.