Incidence and risk of endocrine and metabolic abnormalities linked to PARP inhibitors in solid tumors: a meta-analysis.

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) serve as crucial therapeutic agents in solid tumor treatment. Preclinical investigations suggest a potential protective function of PARPi against endocrine and metabolic impairments. Nevertheless, the existing body of evidence remains inconclusive on this aspect. Purpose: Our aim was to evaluate the potential impact of PARPi on endocrine and metabolic disruptions in clinical trials. Data sources: We conducted a comprehensive search across the Medline, EMBASE, PubMed, and Web of Science databases, along with the ClinicalTrials.gov registry. Study selection: Phase II/III randomized controlled trials (RCTs) investigating the effects of PARPi in metabolic and endocrine processes were selected for inclusion in patients with solid tumors. Data extraction: The primary outcomes of interest encompassed metabolic and endocrine dysfunctions. Data synthesis: A total of 26 trials (n = 9,590 patients) were included in our meta-analysis. Niraparib demonstrated an increased risk of any-grade hyperglycemia (OR = 2.15, 95% CI 1.28–3.62), with patients receiving PARPi for metastatic pancreatic cancer showing a higher susceptibility to any-grade hyperglycemia (OR = 1.78, 95% CI 1.04–3.04). Conversely, rucaparib exhibited a potential ameliorative effect on hyperglycemia (OR = 0.54, 95% CI 0.30–0.97). No statistically significant disparities were observed for other outcomes associated with PARPi utilization. Limitations: Among these RCTs included, 50% were assessed as low qualities due to high risk of bias. Conclusions: Our meta-analysis demonstrated that PARPi may exert adverse effects on endocrine and metabolic pathways. Close monitoring of hyperglycemia is recommended for patients undergoing niraparib therapy, especially those with pancreatic cancer. Trial registration: This meta-Analysis was prospectively registered in the PROSPERO database with ID CRD42023457959. Highlights: Preclinical studies indicate that PARPi may provide protection against endocrine and metabolic abnormalities. This systematic review and meta-analysis aimed to assess the association between PARPi and the incidence of endocrine and metabolic abnormalities in patients with solid tumors. Our findings revealed that PARPi adversely affect both endocrine and metabolic processes in patients with solid tumors. Special attention is warranted regarding hyperglycemia in patients treated with niraparib, particularly those with pancreatic cancer. The underlying mechanisms of PARPi's effects on endocrine and metabolic functions remain unclear, highlighting the need for further comprehensive research. [ABSTRACT FROM AUTHOR]