Hematological Toxicities with PARP Inhibitors in Prostate Cancer: A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials

Author:

Bowling Gartrell C.12ORCID,Swargaloganathan Piragash1,Heintz Carly1ORCID,Madan Ravi A.3,Eldhose Binil24ORCID,Dobi Albert24,Chesnut Gregory T.245

Affiliation:

1. School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20817, USA

2. Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20817, USA

3. Genitourinary Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

4. Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA

5. Urology Service, Walter Reed National Medical Center, Bethesda, MD 20814, USA

Abstract

Background: Poly ADP-ribose polymerase inhibitors (PARPis) are an important class of therapeutics for metastatic castration-resistant prostate cancer (mCRPC). Unlike hormone-based treatments for mCRPC, PARPis are not without drug-related hematological adverse events. Objective: To review the evidence on hematological toxicities, including anemia, thrombocytopenia, and neutropenia from PARPis in prostate cancer. Study Methodology: A systematic review and meta-analysis using the PRISMA guidelines was performed for phase II and III randomized controlled trials (RCTs) of PARPis in prostate cancer. PubMed, Embase, and Ovid All EBM reviews—Cochrane were queried from inception to 9 June 2023. The Mantel–Haenszel method was used to report risk ratios (RR) and 95% confidence intervals (CI) for all-grade and high-grade anemia, thrombocytopenia, and neutropenia toxicities. Results: The systematic review retrieved eight phase II and III RCTs; specifically, eight were included in the anemia, five in the all-grade thrombocytopenia and neutropenia, and four in the high-grade thrombocytopenia and neutropenia outcomes. Compared to a placebo and/or other non-PARPi treatments, PARPi use was associated with an increased risk of all-grade anemia (RR, 3.37; 95% CI, 2.37–4.79; p < 0.00001), thrombocytopenia (RR, 4.54; 95% CI, 1.97–10.44; p = 0.0004), and neutropenia (RR, 3.11; 95% CI, 1.60–6.03; p = 0.0008). High-grade anemia (RR, 6.94; 95% CI, 4.06–11.86; p < 0.00001) and thrombocytopenia (RR, 5.52; 95% CI, 2.80–10.88; p < 0.00001) were also associated with an increased risk, while high-grade neutropenia (RR, 3.63; 95% CI, 0.77–17.23; p = 0.10) showed no significant association. Subgroup stratification analyses showed differences in various all-grade and high-grade toxicities. Conclusion: PARPis were associated with an increased risk of hematological AEs. Future studies with more pooled RCTs will enhance this understanding and continue to inform patient–physician shared decision-making. Future studies may also have a role in improving the current management strategies for these AEs.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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