Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Giulia Russo
,
Maria Antonietta Barbieri
ORCID logo ,
Emanuela Elisa Sorbara
,
Giuseppe Cicala
ORCID logo ,
Tindara Franchina
,
Mariacarmela Santarpia
,
Nicola Silvestris
,
Edoardo Spina
* ORCID logo
Version 1 : Received: 26 July 2023 / Approved: 27 July 2023 / Online: 28 July 2023 (02:34:59 CEST)

A peer-reviewed article of this Preprint also exists.

Russo, G.; Barbieri, M.A.; Sorbara, E.E.; Cicala, G.; Franchina, T.; Santarpia, M.; Silvestris, N.; Spina, E. Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database. Biomedicines 2023, 11, 2311. Russo, G.; Barbieri, M.A.; Sorbara, E.E.; Cicala, G.; Franchina, T.; Santarpia, M.; Silvestris, N.; Spina, E. Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database. Biomedicines 2023, 11, 2311.

Abstract

Background: This study assessed the nephrotoxicity of oral BRAF inhibitors (BRAFi), regorafenib (REG) and encorafenib (ENC), in metastatic colorectal cancer (mCRC), through an analysis of re-ports from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) da-tabase. Methods: A descriptive and disproportional analyses were performed for all reports with ENC and REG as the primary suspect. Results: A total of 379 reports had at least one renal ADR, mainly related to REG (93.1%). Potential safety signals for REG particularly 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 syn-drome (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), dys-uria (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 highlighted some not extensively reported renal ADRs that required further investigations to better characterize the safety profile of BRAFi in patients with mCRC.

Keywords

Colorectal cancer; pharmacovigilance; BRAF inhibitors; regorafenib; encorafenib; adverse drug reactions; renal disorders

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.