Next Article in Journal
Role of Sirtuins in the Pathobiology of Onco-Hematological Diseases: A PROSPERO-Registered Study and In Silico Analysis
Previous Article in Journal
Dietary Inflammatory Index and Mortality from All Causes, Cardiovascular Disease, and Cancer: A Prospective Study
Previous Article in Special Issue
Endocrine Late Effects in Childhood Cancer Survivors
 
 
Article

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System

1
Pharmacology Unit, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum–University of Bologna, 40126 Bologna, Italy
2
Division of Endocrinology and Diabetes Prevention and Care Unit, IRCCS Azienda Ospedaliero–Universitaria di Bologna, 40138 Bologna, Italy
3
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum–University of Bologna, 40138 Bologna, Italy
4
Medical Oncology, IRCCS Azienda Ospedaliero–Universitaria di Bologna, 40138 Bologna, Italy
5
Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Marialuisa Luisa Appetecchia
Cancers 2022, 14(19), 4610; https://doi.org/10.3390/cancers14194610
Received: 2 August 2022 / Revised: 15 September 2022 / Accepted: 19 September 2022 / Published: 22 September 2022
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)
This real-world post-marketing research described clinical features of adrenal insufficiency with anticancer drugs targeting vascular endothelial growth factor receptor reported to the Food and Drug Administration pharmacovigilance database. A robust signal emerged for multi-targeted tyrosine kinase inhibitors, especially in combination with immunotherapy, namely checkpoint inhibitors in renal cancer. These signals should promote both prospective research and a multidisciplinary proactive monitoring by healthcare professionals. These findings strengthen the role of timely pharmacovigilance to detect and characterize post-marketing adverse events of special interest, thus supporting patient care.
Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January 2004–March 2022) were identified through the high-level term “adrenal cortical hypofunctions”. Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs). Results: Out of 147,153 reports with VEGFR-TKIs, 314 cases of AI were retained, mostly of which were serious (97.1%; hospitalization recorded in 44.9%). In a combination regimen with ICIs (43% of cases), VEGFR-TKIs were discontinued in 52.2% of the cases (26% as monotherapy). The median time to onset was 72 days (IQR = 14–201; calculated for 189 cases). A robust disproportionality signal emerged, also in comparison with other anticancer drugs (ROR = 2.71, 95%CI = 2.42–3.04; IC = 0.25, 95%CI = 0.07–0.39). Cabozantinib, sunitinib and axitinib generated robust disproportionality even after ROR adjustment. Conclusions: We call pharmacologists, internists, oncologists and endocrinologists to raise awareness of serious AI with VEGFR-TKIs, and to develop dedicated guidelines, especially for combination regimens with immunotherapy. View Full-Text
Keywords: VEGFR; adrenal insufficiency; pharmacovigilance; disproportionality analysis; FAERS VEGFR; adrenal insufficiency; pharmacovigilance; disproportionality analysis; FAERS
Show Figures

Graphical abstract

MDPI and ACS Style

Raschi, E.; Fusaroli, M.; Giunchi, V.; Repaci, A.; Pelusi, C.; Mollica, V.; Massari, F.; Ardizzoni, A.; Poluzzi, E.; Pagotto, U.; Di Dalmazi, G. Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System. Cancers 2022, 14, 4610. https://doi.org/10.3390/cancers14194610

AMA Style

Raschi E, Fusaroli M, Giunchi V, Repaci A, Pelusi C, Mollica V, Massari F, Ardizzoni A, Poluzzi E, Pagotto U, Di Dalmazi G. Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System. Cancers. 2022; 14(19):4610. https://doi.org/10.3390/cancers14194610

Chicago/Turabian Style

Raschi, Emanuel, Michele Fusaroli, Valentina Giunchi, Andrea Repaci, Carla Pelusi, Veronica Mollica, Francesco Massari, Andrea Ardizzoni, Elisabetta Poluzzi, Uberto Pagotto, and Guido Di Dalmazi. 2022. "Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System" Cancers 14, no. 19: 4610. https://doi.org/10.3390/cancers14194610

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop