Risk of Cardiovascular Toxicity and Hypertension in Prostate Cancer Patients Treated with the Combination of a PARP Inhibitor and Abiraterone: A Systematic Review and Meta-Analysis 

Ciccarese C, Strusi A, Arduini D, Maratta MG, D’Agostino F, Sacco E, Totaro A, Bassi P, Iacovelli R and Tortora G

Medical Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Department of Urology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Università Cattolica del Sacro Cuore, Rome, Italy

^*Correspondance to: Roberto Iacovelli 

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Abstract:

Background: Combinations of an Androgen Receptor Signaling inhibitor (ARSi, i.e., abiraterone acetate) and a PARPi (i.e., olaparib, niraparib) have recently shown to significantly improve clinical outcomes of metastatic Castration–Resistant Prostate Cancer (mCRPC) patients compared to ARSi monotherapy. These combinations have been associated with a potential increased risk of Cardiovascular Toxicity (CVT) and hypertension. We analyzed the incidence and the relative risk of developing CVT and hypertension in mCRPC treated with abiraterone and PARPi.
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 Relative Risks (RRs) and 95% Confidence Intervals (CIs) were calculated using fixed- or random-effects methods, depending on studies heterogeneity. The statistical analyses were performed with RevMan software for meta-analysis (v.5.2.3).
Results: Three articles were selected for this meta-analysis, including a total of 1,361 patients who were used to evaluate the CVT. The incidence of treatment-related CVT of any- and high-grade was 12.7% and 7.4%, respectively. Treatment with the association of abiraterone and a PARPi was associated with a significant increased risk of any grade CVT (RR=1.57, 95% CI 1.14-2.17; p=0.005) but not with high-grade CVT (RR=3.39; p=0.36) compared to abiraterone monotherapy. Moreover, the combination of abiraterone and a PARPi did not significantly increase the risk of hypertension of any grade (RR=1.07; p=0.74) and high-grade (RR=1.11; p=0.60) compared to control.
Conclusion: Treatment with abiraterone associated with a PARPi has a manageable safety profile in terms of cardiac disorders, with a significantly increase of the risk of CVT of any-grade, but not of high-grade, compared to controls. The incidence and relative risk of hypertension of any-grade and high-grade were not significantly augmented by this therapeutic approach.

Keywords:

mCRPC; Prostate cancer; PARPi; Abiraterone; Cardiovascular toxicity; Hypertension

Cite the Article:

Ciccarese C, Strusi A, Arduini D, Maratta MG, D’Agostino F, Sacco E, et al. Risk of Cardiovascular Toxicity and Hypertension in Prostate Cancer Patients Treated with the Combination of a PARP Inhibitor and Abiraterone: A Systematic Review and Meta-Analysis. Clin Oncol. 2022;7:1967..