BRAF and MEK inhibitors rechallenge after an adverse drug reaction in patients with cancer: A pharmacovigilance cohort study
Abstract
IMPORTANCE: The safety profile of a rechallenge with BRAF inhibitors (BRAFi) or a combination of BRAF and MEK inhibitors (MEKi) following an adverse drug reaction (ADR) remains largely unexplored. OBJECTIVE: To identify the reported recurrence rate of the same ADR after a BRAFi±MEKi targeted therapy (TT) rechallenge in patients with cancer and to identify factors associated with recurrence. DESIGN, SETTING, AND PARTICIPANTS: In this observational, pharmacovigilance study, ADR reports were sourced from VigiBase, the World Health Organization database. The inclusion criteria encompassed all BRAFi cases (with or without MEKi) through September 01, 2023, irrespective of the primary cancer diagnosis. MAIN OUTCOMES AND MEASURES: The primary outcome was the reported recurrence rate of the same initial ADR following TT rechallenge. Secondary outcomes measures included were identification of variables associated with recurrence among informative rechallenges, defined as those with known recurrence status. RESULTS: Out of 21,339 ADR cases linked to TT, 4771 (22.4%) reported a rechallenge, with 563 yielding informative data (11.8%). Recurrence of the initial ADR was reported in 223 cases, resulting in a reported recurrence rate of 39.6% (95% CI: 35.7-43.7). The highest recurrence rates in a rechallenge were observed for pyrexia (47%, 95% CI: 39-55), renal failure (46%, 95% CI: 32-60), and musculoskeletal disorders (44%, 95%CI: 33-56). There was no significant influence of factors such as TT regimen (either BRAFi monotherapy or any TT combination), age, sex, or the type of cancer on reported recurrence rate. CONCLUSIONS AND RELEVANCE: In real-world settings, approximately two-fifths of cases with notified TT rechallenges led to a reporting of recurrence of the same initial ADR. The primary determinant of reported recurrence seems to be the nature of the initial ADR rather than the TT regimen, or any other baseline patient characteristic.
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BibTeX
@article{ezine2026braf,
title = {{BRAF and MEK inhibitors rechallenge after an adverse drug reaction in patients with cancer: A pharmacovigilance cohort study}},
author = {Emilien Ezine and Angélique da Silva and Safa Idoudi and Céleste Lebbe and Basile Chrétien and Marion Sassier and Joachim Alexandre and Charles Dolladille},
journal = {Therapies},
year = {2026},
month = sep,
doi = {10.1016/j.therap.2024.12.011},
url = {https://hal.science/hal-05746225v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - BRAF and MEK inhibitors rechallenge after an adverse drug reaction in patients with cancer: A pharmacovigilance cohort study
AU - Emilien Ezine
AU - Angélique da Silva
AU - Safa Idoudi
AU - Céleste Lebbe
AU - Basile Chrétien
AU - Marion Sassier
AU - Joachim Alexandre
AU - Charles Dolladille
PY - 2026
DA - 2026/09/11
JO - Therapies
DO - 10.1016/j.therap.2024.12.011
UR - https://hal.science/hal-05746225v1
AB - IMPORTANCE: The safety profile of a rechallenge with BRAF inhibitors (BRAFi) or a combination of BRAF and MEK inhibitors (MEKi) following an adverse drug reaction (ADR) remains largely unexplored. OBJECTIVE: To identify the reported recurrence rate of the same ADR after a BRAFi±MEKi targeted therapy (TT) rechallenge in patients with cancer and to identify factors associated with recurrence. DESIGN, SETTING, AND PARTICIPANTS: In this observational, pharmacovigilance study, ADR reports were sourced from VigiBase, the World Health Organization database. The inclusion criteria encompassed all BRAFi cases (with or without MEKi) through September 01, 2023, irrespective of the primary cancer diagnosis. MAIN OUTCOMES AND MEASURES: The primary outcome was the reported recurrence rate of the same initial ADR following TT rechallenge. Secondary outcomes measures included were identification of variables associated with recurrence among informative rechallenges, defined as those with known recurrence status. RESULTS: Out of 21,339 ADR cases linked to TT, 4771 (22.4%) reported a rechallenge, with 563 yielding informative data (11.8%). Recurrence of the initial ADR was reported in 223 cases, resulting in a reported recurrence rate of 39.6% (95% CI: 35.7-43.7). The highest recurrence rates in a rechallenge were observed for pyrexia (47%, 95% CI: 39-55), renal failure (46%, 95% CI: 32-60), and musculoskeletal disorders (44%, 95%CI: 33-56). There was no significant influence of factors such as TT regimen (either BRAFi monotherapy or any TT combination), age, sex, or the type of cancer on reported recurrence rate. CONCLUSIONS AND RELEVANCE: In real-world settings, approximately two-fifths of cases with notified TT rechallenges led to a reporting of recurrence of the same initial ADR. The primary determinant of reported recurrence seems to be the nature of the initial ADR rather than the TT regimen, or any other baseline patient characteristic.
SN - 0040-5957
SN - 1958-5578
ER -