European journal of obstetrics, gynecology, and reproductive biology · 2024
Haematological toxicity of PARP inhibitors in advanced ovarian cancer: A systematic review and meta-analysis.
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Pio Maiorano Mauro Francesco, Loizzi Vera, Maiorano Brigida Anna, Cormio Gennaro
Аннотация
BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPis) are effective treatment options for patients with advanced ovarian cancer (OC). A typical adverse event (AE) of these agents is haematological toxicity, which represents the leading cause of treatment modification and discontinuation. This systematic review and meta-analysis aimed to analyse the risk of haematological AEs, including anaemia, neutropenia and thrombocytopenia due to the use of PARPis in patients with OC.
METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. PubMed, EMBASE and Cochrane databases, and international meeting abstracts were searched systematically for clinical trials concerning the use of PARPis in patients with OC. The search deadline was 30 March 2024. The pooled incidence of all grades and grade 3or more (≥G3) anaemia, neutropenia and thrombocytopenia were analysed. Subsequently, risk ratios (RRs) were calculated for all grades and ≥G3 AEs of PARPis compared with non-PARPis from randomized controlled trials.
RESULTS: In total, 12 phase II/III trials with olaparib, niraparib and rucaparib were included in this study. Anaemia was the most common all grade (28.8 %) and ≥G3 (12.1 %) AE. The administration of PARPis increased the risk of developing all grade anaemia [risk ratio (RR) = 2.44], neutropenia (RR = 3.15) and thrombocytopenia (RR = 4.66) significantly compared with non-PARPis. Similarly, a significant increase in the risk of ≥G3 anaemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a non-significant increase in the risk of neutropenia (RR = 3.41) were detected.
CONCLUSIONS: In patients with advanced OC, PARPis increase the risk of haematological toxicity compared with other treatments (high-quality evidence). Clinicians should be aware of this risk and the correct management, as these drugs are highly employed in these patients.
METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. PubMed, EMBASE and Cochrane databases, and international meeting abstracts were searched systematically for clinical trials concerning the use of PARPis in patients with OC. The search deadline was 30 March 2024. The pooled incidence of all grades and grade 3or more (≥G3) anaemia, neutropenia and thrombocytopenia were analysed. Subsequently, risk ratios (RRs) were calculated for all grades and ≥G3 AEs of PARPis compared with non-PARPis from randomized controlled trials.
RESULTS: In total, 12 phase II/III trials with olaparib, niraparib and rucaparib were included in this study. Anaemia was the most common all grade (28.8 %) and ≥G3 (12.1 %) AE. The administration of PARPis increased the risk of developing all grade anaemia [risk ratio (RR) = 2.44], neutropenia (RR = 3.15) and thrombocytopenia (RR = 4.66) significantly compared with non-PARPis. Similarly, a significant increase in the risk of ≥G3 anaemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a non-significant increase in the risk of neutropenia (RR = 3.41) were detected.
CONCLUSIONS: In patients with advanced OC, PARPis increase the risk of haematological toxicity compared with other treatments (high-quality evidence). Clinicians should be aware of this risk and the correct management, as these drugs are highly employed in these patients.