Rechallenge of BRAF +/- MEK Inhibitors Following an Adverse Event in Patients With Cancer (BRAFREC)

Rechallenge of Rapidly Accelerated Fibrosarcoma B-type (BRAF) +/- Mitogen-activated Extracellular Signal-regulated Kinase (MEK) Inhibitors Following an Adverse Event in Patients With Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: BRAF inhibitor

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 Type: Observational
• Enrollment (Anticipated): 16000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population is made of individual case safety reports from the World Health Organization pharmacovigilance database VigiBase, where patients had an adverse event following BRAF+/-MEKi therapy intakes.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

Drug: BRAF inhibitor; Reports of adverse events occurring in patients treated with at least one BRAFi or MEKi as reported in the individual case safety reports.; Other Names: MEK inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate	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	Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of rechallenge and non-rechallenge cases	Baseline characteristics (initial adverse event, cancer indication, age, sex) Measurements are the Medical Dictionary for Regulatory Activities preferred terms for adverse events and cancer indications, the Anatomical and Therapeutical Class for drugs. Age is categorized (18-45, 45-64, 65-74, > 75y.o.), sex (male, female).	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)	Across baseline characteristics (initial adverse event, cancer indication, age, sex). Measurements are the Medical Dictionary for Regulatory Activities preferred terms for adverse events and cancer indications, the Anatomical and Therapeutical Class for drugs. Age is categorized (18-45, 45-64, 65-74, > 75y.o.), sex (male, female). The recurrence is defined as a second occurrence of an initial adverse event after the treatment was reintroduced. It is a dichotomous outcome. Data will be analyzed through a regression model, so as to determinate which of these covariates are associated with a higher recurrence rate.	Up to 10 years
Rate of occurrence of a different AE after a monotherapy or combination therapy rechallenge (among informative rechallenges)	The occurrence rate will be obtained by dividing the number of cases with another AE that occurred following a treatment rechallenge by the number of informative rechallenges and will be expressed as a percentage	Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Investigators: Principal Investigator: Charles Dolladille, University Hospital, Caen

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): March 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 15, 2021

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: BRAFREC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data for this study are available at http://www.vigiacess.org/. Dissemination to study participants / researchers is not possible outside of the dedicated website.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No