Hematological Toxicities with PARP Inhibitors in Prostate Cancer : A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Cancers - 15(2023), 19 vom: 09. Okt. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bowling, Gartrell C [VerfasserIn] |
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| Links: |
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| Themen: |
CRPC |
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| Anmerkungen: |
Date Revised 20.10.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/cancers15194904 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363285598 |
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| 100 | 1 | |a Bowling, Gartrell C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hematological Toxicities with PARP Inhibitors in Prostate Cancer |b A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials |
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| 500 | |a Date Revised 20.10.2023 | ||
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| 520 | |a 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 | ||
| 520 | |a OBJECTIVE: To review the evidence on hematological toxicities, including anemia, thrombocytopenia, and neutropenia from PARPis in prostate cancer | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a PARP inhibitors | |
| 650 | 4 | |a Poly ADP-ribose polymerase (PARP) | |
| 650 | 4 | |a niraparib | |
| 650 | 4 | |a olaparib | |
| 650 | 4 | |a prostate cancer | |
| 650 | 4 | |a rucaparib | |
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| 700 | 1 | |a Heintz, Carly |e verfasserin |4 aut | |
| 700 | 1 | |a Madan, Ravi A |e verfasserin |4 aut | |
| 700 | 1 | |a Eldhose, Binil |e verfasserin |4 aut | |
| 700 | 1 | |a Dobi, Albert |e verfasserin |4 aut | |
| 700 | 1 | |a Chesnut, Gregory T |e verfasserin |4 aut | |
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