Postmarket review of photosensitivity associated with select BRAF and MEK inhibitors

BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are approved in the U.S. to be given in combination or as single agents to treat patients with BRAF V600E/K-positive solid and histiocytic neoplasms. During postmarketing safety surveillance, we identified cases of photosensitivity with BRAFi (dabrafenib, encorafenib) and MEKi (trametinib, binimetinib) and evaluated this finding further using data from the Food and Drug Administration's Adverse Event Reporting System, the literature, and the drug manufacturers. We identified 72 cases of photosensitivity with BRAFi/MEKi with a median time to onset of 60 days. Cases described erythema, pruritis, blistering, pain, and swelling. Based on a temporal relationship; positive dechallenge after BRAFi/MEKi discontinuation, interruption, or dose reduction; and positive rechallenge with drug re-exposure, findings from our case series suggest a causal association between BRAFi/MEKi and photosensitivity, and this is further supported by pre-market, non-clinical testing results.