Outcomes of patients treated with dabrafenib and trametinib who developed pyrexia syndrome and severe/complicated pyrexia syndrome.

Abstract

e24092 Background: The combination of dabrafenib and trametinib has been used to treat many malignancies featuring BRAF mutations. The most common adverse event observed in patients on dabrafenib/trametinib is pyrexia syndrome. Pyrexia syndrome is defined by the Canadian Working Group as fever > 38 o C and/or chills, rigors, night sweats, and flu-like symptoms in the absence of infection. They further defined severe/complicated pyrexia as pyrexia syndrome requiring hospitalization, or complicated by CTCAE grade 2 or higher dehydration, hypotension, renal dysfunction, confusion, or vomiting. Here, we report the incidence of pyrexia and severe/complicated pyrexia associated with dabrafenib/trametinib at the University of Rochester Wilmot Cancer Center, and discuss the potential prognostic significance of pyrexia syndrome. Methods: We collected retrospective data on patients treated with dabrafenib and trametinib between 2015 and 2022. For each patient, we recorded the number of episodes of pyrexia and severe/complicated pyrexia. Additional information was collected on the type of malignancy, duration of therapy, and whether treatment was terminated due to an adverse event or disease progression. For each episode of pyrexia, analysis was performed to rule out infection. All cases for which the presence of infection was ambiguous were reviewed by an infectious disease specialist. Results: We reviewed 109 patients treated at our institution with dabrafenib and trametinib. 88 patients had complete outcomes data and were included in the final analysis. Melanoma was the most common malignancy followed by lung cancer, thyroid cancer, and glioma. 39% of patients developed pyrexia syndrome and 16% developed severe/complicated pyrexia. The median time to development of pyrexia syndrome was 1 month. On average, patients included in our study were on dabrafenib/trametinib for 12 months. Patients who developed pyrexia were more likely than patients who did not develop pyrexia to discontinue therapy due to an adverse event (32% vs 22%), and patients who developed severe/complicated pyrexia were even more likely to discontinue treatment (43%). However, patients who developed pyrexia on average remained on therapy for a longer period than patients who did not develop pyrexia (17 vs 9 months). Furthermore, patients who developed severe/complicated pyrexia remained on therapy for even longer (26 months). Conclusions: Pyrexia syndrome is the most common adverse event in patients treated with dabrafenib and trametinib. While patients who develop pyrexia and severe/complicated pyrexia are more likely to require their medication to be discontinued, they also remain on treatment for longer periods, suggesting that pyrexia may be a positive prognostic marker of treatment efficacy. This speaks to the importance of developing strategies for the management of pyrexia syndrome.