Background: Twelve months of adjuvant oral dabrafenib + trametinib therapy significantly prolonged relapse-free survival versus placebo in patients with resected BRAF V600E/K–mutant stage III melanoma. Adverse events (AEs) led to treatment discontinuation in 26% of patients; pyrexia was most common (9%).
Objectives: Because of the substantial benefit with adjuvant dabrafenib + trametinib, it is important to optimize AE management and adherence to treatment. We present a case to highlight recommendations for pyrexia management.
Methods: We report the case of a patient treated at an academic center and recommendations for pyrexia management with an algorithm based on clinical experience and literature evaluation.
Results: A 60-year-old man presented with resected BRAF V600K–mutant stage IIIC (AJCC 8th edition) melanoma. He was treated with adjuvant dabrafenib 150 mg twice daily plus trametinib 2 mg once daily. At week 6 of treatment, the patient reported grade 1 acneiform rash, grade 1 myalgias, and grade 2 chills and fever (maximum temperature, 103.4°F); dabrafenib and trametinib were held and he was instructed to start ibuprofen 400 mg 3 times/day as needed. The fever persisted, and prednisone 10 mg/day was added. Both dabrafenib and trametinib were withheld until he was asymptomatic for 2 days, then the full dose of dabrafenib and trametinib was resumed while prednisone 10 mg/day was continued. At week 10, the patient remained pyrexia-free, and prednisone was tapered to 5 mg/day. At week 14, prednisone was further reduced to 2.5 mg/day. He has remained without pyrexia through week 20.
This case illustrates the clinical learnings from pyrexia management in patients treated with dabrafenib + trametinib. Although the prescribing information recommends interrupting dabrafenib (but not trametinib) for uncomplicated fever ≤ 104°F, clinical experience indicates that both dabrafenib and trametinib should be interrupted at the first sign of pyrexia or its prodrome. Dose interruption and the administration of corticosteroids are the most effective means of preventing recurrent episodes; dose reductions are less effective. Patient education and communication are cornerstones to proactive AE management.
Conclusion: Proactive management of pyrexia through dose interruption of both dabrafenib and trametinib at the first sign of pyrexia or its prodrome can help effectively manage pyrexia episodes.
Note: This abstract was accepted and previously presented at the 2019 Annual Conference of the Oncology Nursing Society. All rights reserved.