Abstract 1592P
Background
Poly (ADP-ribose) polymerase inhibitors (PARPi) have changed the treatment landscape of several types of solid tumors in the last years, but little is known about their cardiovascular (CV) safety profile. This meta-analysis aimed at assessing the incidence and relative risk (RR) of PARPi-related cardiovascular toxicity (CVT) and hypertension (HTN).
Methods
Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts. Data extraction was conducted according to the PRISMA statement. Combined RRs and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods, depending on studies heterogeneity. RevMan software for meta-analysis (v.5.2.3) was used to perform statistical analyses.
Results
Twenty-two studies were selected for the analysis of CVT, with a total of 7078 patients. The incidence of any grade and high-grade CVT was 6.5% and 2.4% with PARPi, respectively, compared to 3.9% and 1.6% in the controls. Treatment with a PARPi significantly increased the risk of any grade CVT (fixed-effects, RR=1.80, 95% CI 1.42–2.27; p<0.00001) and of high-grade CVT (fixed-effects, RR=1.62, 95% CI 1.15–2.28; p=0.006) compared to controls. Similarly, when considering only those studies testing a PARPi monotherapy in the experimental arms, the risk of CVT of any grade (RR=4.49, p=0.008) and high-grade (RR=3.16, p=0.006) was significantly higher compared to controls. As concern HTN, twenty-one studies were selected, with a total of 8365 patients. The incidence of HTN of any grade and high-grade was 19.2% and 4.7% with PARPi therapies, respectively, compared to 13.7% and 3.3% in the controls. Treatment with a PARPi significantly increased the risk of HTN of any grade compared to controls (random-effects, RR=1.77, 95% CI 1.07–2.92; p=0.03), but not of high-grade (RR=1.61, 95% CI 0.89–2.89; p=0.11). However, PARPi monotherapy was associated with a higher risk of HTN of high-grade (RR=2.33; p =0.0005), but not of any grade (RR 4.30, p =0.07).
Conclusions
PARPi significantly increase the risk of developing CVT and HTN. Therefore, clinicians should take into account patient's CV comorbidities and accurately monitor, early recognize and manage treatment-related CV complications.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.