title: Pancreatitis with vascular endothelial growth factor receptor tyrosine kinase inhibitors.
abstract: A trial-level meta-analysis was conducted to determine the relative risk (RR) of pancreatitis associated with multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without an FDA-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib, regorafenib). Statistical analyses calculated the RR and 95% confidence intervals (CI). A total of 10,578 patients from 16 phase III trials and 6 phase II trials were selected. The RR for all grade and high-grade pancreatitis for the TKI vs. no TKI- arms was 1.95 (p=0.042, 95% CI: 1.02 to 3.70) and 1.89 (p=0.069, 95% CI: 0.95 to 373), respectively. No differential impact of malignancy type or specific TKI agent was seen on RR of all grade of high grade pancreatitis. Better patient selection and monitoring may mitigate the risk of severe pancreatitis.
authors.affiliation: Department of Internal Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Ghatalia
authors.affiliation: Department of Biostatistics, UAB School of Public Health, Birmingham, AL, USA.
authors.forename: Charity J
authors.initials: CJ
authors.lastname: Morgan
authors.affiliation: Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Medicine, Hospital Del Mar, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Rocha
authors.affiliation: Department of Internal Medicine, Section of Medical Oncology, UAB Medical Center, Birmingham, AL, USA.
authors.forename: Gurudatta
authors.initials: G
authors.lastname: Naik
authors.affiliation: Department of Internal Medicine, Section of Medical Oncology, UAB Medical Center, Birmingham, AL, USA. Electronic address: gsonpavde@uabmc.edu.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D016017:Odds Ratio; D010195:Pancreatitis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Approved; Meta-analysis; Pancreatitis; Tyrosine kinase inhibitors; Vascular endothelial growth factor receptor