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Updated: Sep 17, 2025
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
Peripheral neuropathies induced by BRAF+MEK inhibitor combinations: a real-world study based on FAERS database
Yuting Wang1, Jingping Zheng1, Zhenpo Zhang1
1School of Pharmaceutical Sciences, Jinan University, Guangzhou, Guangdong, China.
Background:
BRAF/MEK inhibitors (BRAFi+MEKi) like may cause peripheral neuropathies (PN). This study analyzes FAERS data to assess PN signals across BRAFi+MEKi combinations.
Research Design And Methods:
Disproportionality analysis was conducted to quantify the signals of BRAFi+MEKi-associated PN on FAERS database from January 2011 to December 2022. Additionally, we examined the onset times and prognosis of BRAFi+MEKi-associated PN.
Results:
A total of 268 reports of BRAFi+MEKi-associated PN were identified in the study, with a median age range of 60.00 to 69.00 years. All three combination therapies exhibited positive signals for PN, and notably, Encorafenib and Binimetinib (E+B) displayed the strongest association with PN (ROR 3.05[2.47,3.76], IC1.57[1.26]). The associations between PN and different BRAFi+MEKi combinations remained persisted in the gender and age stratification analysis, with all three combination therapies showing an elevated number of disproportionality signals in males compared to females.
Conclusion:
According to our findings, BRAFi+MEKi-associated PN tends to occur several months after initiation and may lead to serious outcomes. Male sex is more likely to be a risk factor associated with PN. Prompt identification and intervention for BRAFi+MEKi-associated PN are crucial, and additional fundamental research is required to validate the underlying mechanism as observed in our study.
Insights
BRAF/MEK inhibitors (BRAFi+MEKi) can cause peripheral neuropathy (PN). Encorafenib and Binimetinib showed the strongest association, with males being a higher risk factor. Early detection and intervention are crucial.
Area of Science:
- Pharmacovigilance
- Oncology
- Neurology
Background:
- BRAF/MEK inhibitors (BRAFi+MEKi) are used in cancer therapy.
- Peripheral neuropathy (PN) is a potential side effect of BRAFi+MEKi.
- This study investigates PN signals associated with BRAFi+MEKi combinations.
Purpose of the Study:
- To assess peripheral neuropathy (PN) signals across different BRAF/MEK inhibitor (BRAFi+MEKi) combinations.
- To analyze the onset times and prognosis of BRAFi+MEKi-associated PN.
- To identify risk factors for BRAFi+MEKi-induced PN.
Main Methods:
- Utilized the FDA Adverse Event Reporting System (FAERS) database.
- Conducted disproportionality analysis from January 2011 to December 2022.
- Performed age and gender stratification analysis.
Main Results:
- Identified 268 reports of BRAFi+MEKi-associated PN.
- Encorafenib and Binimetinib (E+B) demonstrated the strongest PN association (ROR 3.05).
- Males showed a higher incidence of PN signals compared to females.
Conclusions:
- BRAFi+MEKi-associated PN can occur months after treatment initiation and lead to serious outcomes.
- Male sex is identified as a potential risk factor for PN.
- Urgent identification, intervention, and further research into underlying mechanisms are recommended.
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