BRAF and MEK Inhibitors and Their Toxicities: A Meta-Analysis
Mattia Garutti1, Melissa Bergnach2, Jerry Polesel3
1CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy.
Purpose:
This meta-analysis summarizes the incidence of treatment-related adverse events (AE) of BRAFi and MEKi.
Methods:
A systematic search of Medline/PubMed was conducted to identify suitable articles published in English up to 31 December 2021. The primary outcomes were profiles for all-grade and grade 3 or higher treatment-related AEs, and the analysis of single side effects belonging to both categories.
Results:
The overall incidence of treatment-related all-grade Aes was 99% for Encorafenib (95% CI: 0.97-1.00) and 97% for Trametinib (95% CI: 0.92-0.99; I2 = 66%) and Binimetinib (95% CI: 0.94-0.99; I2 = 0%). In combined therapies, the rate was 98% for both Vemurafenib + Cobimetinib (95% CI: 0.96-0.99; I2 = 77%) and Encorafenib + Binimetinib (95% CI: 0.96-1.00). Grade 3 or higher adverse events were reported in 69% of cases for Binimetinib (95% CI: 0.50-0.84; I2 = 71%), 68% for Encorafenib (95% CI: 0.61-0.74), and 72% for Vemurafenib + Cobimetinib (95% CI: 0.65-0.79; I2 = 84%). The most common grade 1-2 AEs were pyrexia (43%) and fatigue (28%) for Dabrafenib + Trametinib and diarrhea for both Vemurafenib + Cobimetinib (52%) and Encorafenib + Binimetinib (34%). The most common AEs of grade 3 or higher were pyrexia, rash, and hypertension for Dabrafenib + Trametinib (6%), rash and hypertension for Encorafenib + Binimetinib (6%), and increased AST and ALT for Vemurafenib + Cobimetinib (10%).
Conclusions:
Our study provides comprehensive data on treatment-related adverse events of BRAFi and MEKi combination therapies, showing related toxicity profiles to offer a helpful tool for clinicians in the choice of therapy.
Insights
This meta-analysis details the high incidence of adverse events (AE) associated with BRAF kinase inhibitors (BRAFi) and MEK inhibitors (MEKi). Clinicians can use this toxicity profile data to guide treatment decisions for patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Medicine
Background:
- BRAF kinase inhibitors (BRAFi) and MEK inhibitors (MEKi) are crucial targeted therapies for various cancers.
- Understanding their associated adverse events (AE) is vital for patient safety and treatment optimization.
Purpose of the Study:
- To systematically summarize the incidence and profiles of treatment-related adverse events (AE) for BRAFi and MEKi therapies.
- To analyze both all-grade and high-grade (grade 3 or higher) adverse events.
Main Methods:
- A comprehensive systematic literature search was performed using Medline/PubMed.
- Articles published in English up to December 31, 2021, were included.
- Primary outcomes focused on AE profiles and specific side effect frequencies.
Main Results:
- All-grade treatment-related AEs were highly frequent, reaching 99% for Encorafenib and 97% for Trametinib.
- High-grade (≥3) AEs were reported in 69% for Binimetinib, 68% for Encorafenib, and 72% for Vemurafenib + Cobimetinib.
- Common AEs included pyrexia, fatigue, diarrhea, rash, hypertension, and elevated liver enzymes (AST/ALT).
Conclusions:
- This meta-analysis provides extensive data on the toxicity profiles of BRAFi and MEKi therapies.
- The findings serve as a valuable resource for clinicians when selecting appropriate treatment strategies.
- Understanding these AE profiles aids in managing patient care and optimizing therapeutic outcomes.
