Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database

Giulia Russo; Maria Antonietta Barbieri; Emanuela Elisa Sorbara; Giuseppe Cicala; Tindara Franchina; Mariacarmela Santarpia; Nicola Silvestris; Edoardo Spina

doi:10.3390/biomedicines11082311

Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database

Biomedicines. 2023 Aug 20;11(8):2311. doi: 10.3390/biomedicines11082311.

Authors

Giulia Russo¹, Maria Antonietta Barbieri¹, Emanuela Elisa Sorbara¹, Giuseppe Cicala¹, Tindara Franchina², Mariacarmela Santarpia², Nicola Silvestris², Edoardo Spina¹

Affiliations

¹ Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
² Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, 98125 Messina, Italy.

Abstract

Background: this study assessed the nephrotoxicity of regorafenib (REG) and encorafenib (ENC) in metastatic colorectal cancer (mCRC) through an analysis of reports from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) database.

Methods: descriptive and disproportional analyses were performed for all reports using ENC and REG as the primary suspect.

Results: A total of 379 reports had at least one renal adverse drug reaction (ADR), and these ADRs were mainly related to REG (93.1%). Potential safety signals for REG included chromaturia (n = 44; ROR = 12.00, CI 95% = 8.92-16.16; IC = 2.36, IC₀₂₅-IC₀₇₅ = 2.06-2.66), hydronephrosis (10; 8.70, 4.67-16.19; 1.85, 1.23-2.47), nephrotic syndrome (7; 5.73, 2.73-12.03; 1.47, 0.73-2.21), renal impairment (53; 4.16, 3.17-5.45; 1.39, 1.12-1.66), dysuria (19; 3.06, 1.95-4.81; 1.06, 0.61-1.52), renal failure (38; 1.66, 1.20-2.28; 0.49, 0.17-0.81), and acute kidney injury (AKI) (43; 1.46, 1.08-1.97; 0.37, 0.07-0.67). For ENC, consistent disproportionalities were observed for AKI (n = 11; ROR = 3.79, CI 95% = 2.09-6.90; IC = 1.32, IC₀₂₅-IC₀₇₅ = 0.72-1.91) and dysuria (4; 6.50, 2.43-17.39; 1.86, 0.88-2.85).

Conclusions: these findings highlight some not extensively reported renal ADRs that require further investigations to better characterize the safety profiles of REG and ENC in patients with mCRC.

Keywords: adverse drug reactions; colorectal cancer; encorafenib; pharmacovigilance; regorafenib; renal disorders; tyrosine kinase inhibitors.

Grants and funding

This research received no external funding.