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

• Published in: BMC cancer Vol. 25; no. 1; pp. 183 - 13
• Main Authors: Fu, Shunlian, Zou, Pingjin, Fang, Zengyi, Zhou, Xinxiang, Chen, Junyang, Gong, Cuicui, Quan, Li, Lin, Bing, Chen, Qiu, Lang, Jinyi, Chen, Meihua
• Format: Journal Article
• Language: English
• Published: London BioMed Central 31.01.2025; BioMed Central Ltd; BMC
• Subjects: Analysis; Antimitotic agents; Antineoplastic agents; Bias; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cancer therapies; Care and treatment; Clinical trials; Diabetes; Diagnosis; Disease susceptibility; Dosage and administration; Endocrine and metabolic abnormalities; Endocrine System Diseases - chemically induced; Endocrine System Diseases - epidemiology; Health Promotion and Disease Prevention; Humans; Hyperglycemia; Hyperthyroidism; Hypoglycemia; Hypothyroidism; Incidence; Intervention; Medicine/Public Health; Meta-analysis; Metabolic diseases; Metabolic Diseases - chemically induced; Metabolic Diseases - epidemiology; Metabolic disorders; Metabolic pathways; Metabolism; Metastases; Neoplasms - drug therapy; Oncology; Ovarian cancer; Pancreatic cancer; PARP inhibitors; Patients; Poly(ADP-ribose) Polymerase Inhibitors - adverse effects; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Prostate; Randomized Controlled Trials as Topic; Risk factors; Software; Solid tumors; Statistical analysis; Surgical Oncology; Systematic Review; Tumors; China; Endocrine and metabolic abnormalities; PARP inhibitors; Meta-analysis
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-025-13579-1

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. Graphical Abstract 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.