Skip to main content

ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1413154
This article is part of the Research Topic Emerging Trends in Real-World Pharmacoepidemiology: 2023 View all 8 articles

Tumor lysis syndrome signal with the combination of encorafenib and binimetinib for malignant melanoma: a pharmacovigilance study using data from the FAERS database

Provisionally accepted
Shuang Xia Shuang Xia 1,2,3Jing-Wen Xu Jing-Wen Xu 4Kang-Xin Yan Kang-Xin Yan 5Yoshihiro Noguchi Yoshihiro Noguchi 6Mayur Sarangdhar Mayur Sarangdhar 7,8,9Miao Yan Miao Yan 1,2,3*
  • 1 Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
  • 2 International Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, China
  • 3 Toxicology Counseling Center of Hunan Province, Changsha, Anhui Province, China
  • 4 Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • 5 Yali High School, Changsha, Anhui Province, China
  • 6 Gifu Pharmaceutical University, Gifu, Gifu, Japan
  • 7 Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States, Cincinnati, Ohio, United States
  • 8 Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States, Cincinnati, Ohio, United States
  • 9 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States, Cincinnati, Ohio, United States

The final, formatted version of the article will be published soon.

    Objective: To investigate the potential association between tumor lysis syndrome (TLS) and drugs for the treatment of malignant melanoma (MM).Methods: Reports of TLS recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004-2023q3) were identified. Demographic and clinical characteristics were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC). The latency of TLS with anticancer drugs was described based on parametric models. Subgroup analysis was conducted to explore the differences of TLS signals in different age and sex.Results: We found 5(1.49%), 59(17.61%), 79(23.58%), 19(5.67%), 13(3.88%), 13(3.88%), 33(9.85%), 49(14.63%), 16(4.78%) TLS reports with pembrolizumab, nivolumab , ipilimumab, dabrafenib, vemurafenib, dacarbazine, "encorafenib and binimetinib" , "nivolumab and ipilimumab" , "dabrafenib and trametinib", respectively. The combination of encorafenib and binimetinib showed the strongest signal of TLS (IC 025 =3.98). The median days of latency of TLS with combination of encorafenib and binimetinib is 2days, which was much shorter than nivolumab (22.0days) and ipilimumab (21.5days). TLS cases associated with drugs for MM were predominantly recorded in females and aged 25-65 years. After excluding confounding factors such as pre-existing diseases and co-treated drugs, the disproportionate signal of TLS with "encorafenib and binimetinib" remained strong..Stronger disproportionate signal of TLS was detected in MM patients using the combination of encorafenib and binimetinib than other drugs. Further research is needed to investigate the underlying mechanisms and identify patient-related predisposing factors to support safe prescribing of the combination of encorafenib and binimetinib.

    Keywords: encorafenib, Binimetinib, Tumor Lysis Syndrome, malignant melanoma, Pharmacovigilance, FAERS, Disproportionality analysis

    Received: 06 Apr 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Xia, Xu, Yan, Noguchi, Sarangdhar and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Miao Yan, Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.