Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

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