Abstract Number: PB1113
Meeting: ISTH 2021 Congress
Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) are anticancer drugs that blocked PARP-1 auto-PARylation. As PARP-1 possesses pro-inflammatory functions involved in the thrombotic process (e.g. expression of adhesion molecules, production of pro-inflammatory cytokines), we hypothesized that PARPis could prevent the development of vascular occlusive events (VOEs).
Aims: To investigate the risk of VOE in patients with cancers treated with PARPis in randomized clinical trials (RCTs).
Methods: The literature search (data lock point: April 17, 2020) was conducted according to a registered protocol (PROSPERO CRD42020179676). All RCTs comparing a PARPi versus placebo or standard of care (SoC) for cancer treatment were included. Two independent investigators were responsible of the screening, the review and the data extraction.
The meta-analysis was performed using a random (REM) and a fixed (FEM) effect model according to the characteristics of the included studies. ORs with 95% CIs were computed using the Peto method for the analysis of VOE and the Mantel-Haenszel method for progression-free survival (PFS) and overall survival (OS). Publication bias was assessed by funnel plots.
Results: Among the 2424 abstracts identified, 13 RCTs fulfilled established criteria. Overall, 2.78% (84/3028) of patients developed a VOE with a PARPi compared with 1.94% (30/1549) in the control group (FEM ORPETO 1.40; 95% CI, 0.94-2.09). This result is consistent whatever the comparator (i.e. placebo and SoC). PARPis significantly improve PFS (REM ORM-H 1.70; 95% CI, 1.10-2.61). This difference is non-significant when PARPis are compared to SoC (REM ORM-H 0.86; 95% CI, 0.64-1.14). OS was not significantly improved with the use of PARPis compared to controls (REM ORM-H 1.13; 95% CI, 0.98-1.31). Funnel plots demonstrate no evidences of publication bias.
Conclusions: Our meta-analysis indicates a tendency toward an increased risk of VOE with PARPis compared to SoC or placebo, requiring careful pharmacovigilance activities of these treatments.
To cite this abstract in AMA style:Haguet H, Ronvaux L, Douxfils J. Risk of Vascular Occlusive Events with PARPis in Cancer: A Systematic Review and Meta-analysis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/risk-of-vascular-occlusive-events-with-parpis-in-cancer-a-systematic-review-and-meta-analysis/. Accessed May 19, 2022.
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