Rechallenge of Rapidly Accelerated Fibrosarcoma B-type (BRAF) +/- Mitogen-activated Extracellular Signal-regulated Kinase (MEK) Inhibitors Following an Adverse Event in Patients With Cancer
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- University Hospital, Caen
- Enrollment
- 16,000
- Primary Endpoint
- Recurrence rate
Study Overview
Brief Summary
Very little data are published on the safety of a rechallenge with a BRAF inhibitor or combination of BRAF and MEK inhibitor (BRAFi and MEKi) after an adverse event (AE). This study aimed at identifying the recurrence rate of the same AE after a BRAFi +/- MEKi rechallenge in patients with cancer and the factors associated to the recurrence.
Detailed Description
This is an observational, cross-sectional, pharmacovigilance cohort study. AEs were extracted from safety reports from the World Health Organization database VigiBase®, to evaluate the safety of a rechallenge with a BRAF inhibitor or combination of BRAF and MEK inhibitor (BRAFi and MEKi) after an adverse event (AE) in patients with cancer.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •All consecutive AE cases associated with BRAFi and MEKi therapy. Combination therapy cases, where BRAFi were concurrently reported with MEKi will be identified, as well as the combination therapy regimen (V+C, D+T, E+B). We will not study MEKi monotherapy cases
Exclusion Criteria
- •MEKi monotherapy cases
- •Cases concurrently reporting on immune checkpoint inhibitor therapies
Arms & Interventions
Reports of adverse events associated with the use of BRAF +/- MEK inhibitors
Reports of adverse event (individual case safety reports) from Vigibase, the World Health Organization pharmacovigilance database related to the use of BRAF +/- MEK inhibitors from inception (1986) until March, 1, 2021 will be extracted.
Cases concurrently reporting on immune checkpoint inhibitor therapies will be excluded.
Intervention: BRAF inhibitor (Drug)
Outcomes
Primary Outcomes
Recurrence rate
Time Frame: Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years
The primary outcome is the rate of recurrence of the same AE after a BRAFi+/- MEKi rechallenge among informative rechallenges The recurrence rate will be obtained by dividing the number of cases with an AE recurrence by the number of informative rechallenges and will be expressed as a percentage
Secondary Outcomes
- Comparison of rechallenge and non-rechallenge cases(Up to 10 years)
- Factors associated with the recurrence after a rechallenge among informative rechallenges (i.e. variables associated with a higher recurrence rate, in a regression model)(Up to 10 years)
- Rate of occurrence of a different AE after a monotherapy or combination therapy rechallenge (among informative rechallenges)(Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years)