title: Metastatic BRAF K601E-mutated melanoma reaches complete response to MEK inhibitor trametinib administered for over 36 months.
abstract: BACKGROUND
  The BRAF K601E mutation occurs in 5% of patients with melanoma, and is the third most common type of BRAF mutation. However, treatment with BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is only approved in patients with BRAF V600-positive melanoma, and patients with K601E-mutated melanoma do not have access to such drugs.
  
  
  METHODS
  A female patient was diagnosed with high tumor burden metastatic melanoma harboring the BRAF K601E mutation. After chemotherapy failure, she underwent compassionate treatment with trametinib. Trametinib showed good activity and efficacy, with 48% shrinkage of a metastatic lymphadenopathy after 4 months' treatment. However, the patient reported treatment-related skin toxicity that required dosage reduction and a personalized intermittent trametinib dosing schedule. After over 36 months from the first trametinib administration, and resection of a metastatic lymphadenopathy, the patient experienced complete response.
  
  
  CONCLUSIONS
  This case report shows that trametinib could be a valid therapeutic option in patients with metastatic melanoma harboring the rare BRAF K601E mutation.
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Via Roma 67, 56100 Pisa, Italy.
authors.forename: Riccardo
authors.identifier: 0000-0001-5120-911X
authors.initials: R
authors.lastname: Marconcini
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Via Roma 67, 56100 Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Galli
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Via Roma 67, 56100 Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antonuzzo
authors.affiliation: Department of Oncology, Ospedale Civile-Istituto Toscano Tumori, Livorno, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bursi
authors.affiliation: Diagnostic and Interventional Radiology, University of Pisa, Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Roncella
authors.affiliation: Units of Pathological Anatomy, Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
authors.affiliation: Units of Pathological Anatomy, Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sensi
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Via Roma 67, 56100 Pisa, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
keywords: BRAF K601E mutation; Complete response; Melanoma; Trametinib