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

Gartrell C Bowling; Piragash Swargaloganathan; Carly Heintz; Ravi A Madan; Binil Eldhose; Albert Dobi; Gregory T Chesnut

doi:10.3390/cancers15194904

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

Cancers (Basel). 2023 Oct 9;15(19):4904. doi: 10.3390/cancers15194904.

Authors

Gartrell C Bowling^{1

2}, Piragash Swargaloganathan¹, Carly Heintz¹, Ravi A Madan³, Binil Eldhose^{2

4}, Albert Dobi^{2

4}, Gregory T Chesnut^{2

4

5}

Affiliations

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.

Keywords: CRPC; PARP inhibitors; Poly ADP-ribose polymerase (PARP); niraparib; olaparib; prostate cancer; rucaparib; talazoparib; veliparib.

Publication types

Review

Grants and funding

This research received no external funding.