COMBI-APlus: Open-label, Phase IIIb Study of Dabrafenib in COMBInation With Trametinib in the Adjuvant Treatment of Stage III BRAF V600 Mutation-positive Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes of an Adapted Pyrexia AE-management Algorithm (Plus)

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This was an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk cutaneous melanoma were screened for eligibility. This study consisted of two periods: 1. Treatment Period - patients received up to 12 months of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily). In the adapted pyrexia management algorithm, dabrafenib and trametinib were interrupted promptly at the onset of pyrexia (≥38°C) and were restarted upon the improvement of symptoms at the same dose if patients remained symptom free (temperature \<38°C) for at least 24 hours. In addition, dabrafenib and trametinib could be interrupted in the presence of pyrexia syndrome (i.e. chills, rigours, night sweats, or influenza-like symptoms) without documented temperature ≥38°C for cases of suspected recurrent pyrexia, at the investigators' discretion. 2. Follow-up Period - patients were followed for disease relapse through 24 months from first dose date. Moreover, patients were followed for overall survival through withdrawal, lost to follow-up, death, or the end of study, whichever occurs first. The follow-up period started once treatment was completed or treatment was prematurely discontinued.