Venous thromboembolic event risk with PARP inhibitors in solid tumors: a systematic review and meta-analysis

Poly (ADP-ribose) polymerase inhibitors (PARPi) are linked to thrombotic events, but the thrombosis risk in various cancers is unclear. This study evaluates the incidence and risk of venous thromboembolic events (VTEs) in patients with solid tumors treated with PARPi.

This meta-analysis included randomized controlled phase II and III clinical trials in which patients with prostate, breast, ovarian, pancreatic, glioblastoma, small-cell lung (SCLC), and non-small-cell lung (NSCLC) cancers were treated with PARPi as monotherapy or in combination. The primary endpoint was to assess the frequency and risk of VTEs in patients treated with PARPi, while the secondary endpoint compared the incidence across different cancer subtypes.

The analysis included 15 008 patients from 38 studies: 8805 in the PARPi group and 6203 in the control group. There were 11 ovarian cancer (n = 4348), 8 prostate cancer (n = 3872), 9 breast cancer (n = 4448), 4 NSCLC (n = 1063), and 3 SCLC (n = 583) studies, and 1 study each for pancreatic cancer (n = 50), glioblastoma (n = 123), and gastric (n = 521) cancer. The incidence of any-grade VTEs with PARPi was observed to be 2.4%, compared with 1.6% in controls, suggesting a possible increase in risk [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.00-1.88, P = 0.050]. This association appeared to be more pronounced in patients with prostate cancer (OR 1.98, 95% CI 1.06-3.70, P = 0.030) and pancreatic cancer (OR 7.22, 95% CI 1.40-37.25, P = 0.020).

While our findings indicate a possible association between PARPi and VTE risk in certain cancer types, this risk appears to be influenced by factors such as cancer subtype and treatment combinations. The overall contribution of PARPi monotherapy to VTE risk may be limited, and the results should be interpreted with caution due to study heterogeneity, wide CIs, and the absence of patient-level data.