encorafenib and Fever

Tremendous progress has been made in the clinical landscape of advanced-stage. Targeted therapy with BRAF plus MEK inhibitors has become the standard of care for patients with advanced-stage

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Azetidines; Benzimidazoles; Carbamates; Fever; Humans; Imidazoles; Indoles; Melanoma; Mitogen-Activated Protein Kinase Kinases; Oximes; Piperidines; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skin Diseases; Sulfonamides; Vemurafenib

Various serious adverse events (AE) have been reported to occur at a high rate in patients treated with BRAF plus mitogen-activated protein kinase kinase (MEK) inhibitor combination therapy, but their subtypes differ among the BRAF/MEK inhibitors. Pyrexia or a spike of fever are well-known AE of BRAF inhibitors, with or without MEK inhibitors, and have been reported to have a high incidence after dabrafenib/trametinib, but not after encorafenib/binimetinib. In this report, we describe three cases of severe pyrexia in nivolumab-resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib. Interestingly, in all cases, the serum levels of soluble CD163 C-X-C motif chemokine (CXCL)9, CXCL10 and CXCL11, which are known biomarkers for adult-onset Still's disease (AOSD), increased in parallel with the development of pyrexia. Our present cases suggest that pyrexia caused by BRAF/MEK inhibitors may possess a similar pathophysiology as that of AOSD.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Drug Resistance, Neoplasm; Female; Fever; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Nivolumab; Positron Emission Tomography Computed Tomography; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Sulfonamides; Treatment Outcome