Systematic review and meta-analysis of cardiovascular safety of poly(ADP-ribose) polymerase inhibitors (PARPis) in cancer
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- BACKGROUND: PARPis are anticancer treatments that have been first explored in the treatment of recurrent ovarian cancer. They have an anti-inflammatory role and a potentially safe cardiovascular profile that may be of interest in patients at risk of cancer-associated thrombosis. OBJECTIVE: to establish if PARPi therapies lead to a better cardiovascular safety in terms of vascular occlusive events independently of the type of cancer, compared to comparators used in clinical trials. DATA SOURCES: one reviewer selected studies from different databases from their inception to April 17, 2020. A trial register and abstracts published during the past three years at international congresses were also searched. STUDY SELECTION: two independent reviewers screened abstracts and titles against inclusion criteria. Overall, 31 abstracts, articles and studies (for a total of 13 randomized clinical trials) were included in the meta-analysis. DATA EXTRACTION: two investigators independently extracted data using a standard form. MAIN OUTCOMES: information extracted included study and patients characteristics, type of intervention, data on vascular occlusive events, progression-free survival (PFS) and overall survival (OS). RESULTS: thirteen randomized clinical trials (3028 patients) were analyzed. Risk of vascular occlusive events was not decreased with PARPis compared to control treatment. In contrast, even if no statistical significance was found, the trend emerging from the meta-analysis was an increase in the rate of vascular occlusive events in the PARPi group (FEM ORPETO 1.40; 95% CI, 0.94- 2.09). PARPis increased PFS compared with controls (REM ORM-H 2.35; 95% CI, 1.44-3.84). No statistical difference in overall survival was found (REM ORM-H 1.13; 95% CI, 0.98-1.31). CONCLUSION: PARPis do not decrease vascular occlusive events. PARPis improve PFS but not the overall survival in patients with any cancer.