Comparative safety analysis of bevacizumab and alkylating agent in glioblastoma management - What have we learned recently?

in Frontiers in pharmacology by Zhizhao Qu, Jiajia Zhao, Liu Yang, Yuanwei Fu, Rui Bai, Jinchuan Li, Hongqin Wang

TLDR

  • The study compared the safety profiles of bevacizumab and alkylating agents in treating glioblastoma and found that bevacizumab has a distinct safety profile with a lower incidence of hematological adverse events.

Abstract

Alkylating agents and bevacizumab are both first-line chemotherapeutic options for the treatment of glioblastoma; however, their mechanisms of action differ substantially. This study aimed to compare the safety profiles of these two drug classes in the treatment of glioblastoma to inform clinical decision-making. Adverse events reported between the first quarter of 2004 and the fourth quarter of 2023 were analyzed using data from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis was employed to assess and compare the AE signals associated with bevacizumab and alkylating agents. In the context of glioblastoma treatment, 3,323 adverse reports were associated with bevacizumab, 5,283 with temozolomide, and 427 with lomustine. The most frequently reported AEs for bevacizumab were fatigue (n = 276), hypertension (n = 220), and headache (n = 199). Compared to temozolomide, bevacizumab was more strongly associated with "vascular disorders," "renal and urinary disorders," and "hypertension." Notably, bevacizumab appeared to offer a potential safety advantage with respect to hematological adverse events. Our analysis indicates that bevacizumab exhibits a distinct safety profile compared to alkylating agents, particularly demonstrating a lower incidence of hematological adverse events. Further prospective studies are warranted to validate these findings and to elucidate the underlying mechanisms responsible for the observed adverse events.

Overview

  • The study aimed to compare the safety profiles of bevacizumab and alkylating agents in the treatment of glioblastoma.
  • The study analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between 2004 and 2023.
  • The primary objective was to inform clinical decision-making by comparing the safety profiles of the two drug classes.

Comparative Analysis & Findings

  • Bevacizumab was more strongly associated with 'vascular disorders', 'renal and urinary disorders', and 'hypertension' compared to temozolomide.
  • Bevacizumab showed a lower incidence of hematological adverse events compared to alkylating agents.
  • The most frequent adverse events reported for bevacizumab were fatigue, hypertension, and headache.

Implications and Future Directions

  • Further prospective studies are needed to validate the findings and elucidate the underlying mechanisms responsible for the observed adverse events.
  • The study's findings may inform clinical decision-making by highlighting the distinct safety profiles of bevacizumab and alkylating agents.
  • Future research should focus on identifying factors that contribute to the differences in safety profiles between the two drug classes.