Incidence and management of pyrexia syndrome in patients treated with dabrafenib and trametinib: a retrospective study

The combination of dabrafenib and trametinib has been used to treat a variety of cancers featuring BRAF mutations. The most common adverse effect is pyrexia syndrome. We aimed to determine the incidence of pyrexia syndrome and severe/complicated pyrexia syndrome and investigate outcomes associated with pyrexia syndrome as well as pyrexia management. In this retrospective cohort study, individuals who received dabrafenib and trametinib from 2015 to 2022 at a large academic medical center were identified. Chart review was performed to determine if patients developed pyrexia syndrome, the severity of pyrexia syndrome, time of onset of pyrexia, time on treatment, how pyrexia was managed, and why treatment was discontinued. 88 patients were included in the final analysis. 34 patients (38.6%) developed pyrexia syndrome and 14 patients (15.9%) developed severe/complicated pyrexia syndrome. Most patients who developed pyrexia syndrome did so in their first month of treatment. Patients who developed pyrexia syndrome were more likely to discontinue treatment due to an adverse event than patients who did not (32.3% vs 22.2%). Patients who developed pyrexia syndrome spent a longer mean period on treatment (16.9 months) than patients who did not (9.0 months). Pyrexia syndrome was managed with dose modifications and interruptions and several agents including steroids, antipyretics, and colchicine. Pyrexia syndrome is a common adverse event in patients on dabrafenib and trametinib. Patients who develop pyrexia syndrome unexpectedly stayed on treatment longer in our cohort, highlighting the importance of early recognition and supportive management to maintain patients on therapy.