title: Safety of vemurafenib in patients with BRAFV600mutated metastatic melanoma: the Spanish experience.
abstract: OBJECTIVE
  Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAFV600mutated advanced melanoma. We investigated safety, tolerability and efficacy of vemurafenib in Spanish patients participating in that study.
  
  
  METHODS
  Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAFV600mutation-positive melanoma received vemurafenib 960 mg twice daily until disease progression, unacceptable toxicity, withdrawal of consent or death. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  301 Spanish patients were included, 70 % with M1c disease, 22 % with brain metastases and 51 % with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48 %), arthralgia (45 %), rash (41 %), photosensitivity (34 %) and skin neoplasms (21 %). Grade 3/4 adverse events occurred in 156 patients (52 %), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16 %), fatigue (6 %) and arthralgia (5 %). The ORR was 28 % (95 % CI 23-34 %). Responses occurred in patients with brain metastases (18 %), elevated baseline lactate dehydrogenase (19 %) and poor performance status (15 %), and elderly patients (22 %). Median PFS was 5.8 (95 % CI 5.0-6.4) months; median OS was 10.5 (95 % CI 9.5-13.5) months.
  
  
  CONCLUSIONS
  Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment.
authors.affiliation: Hospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. AMARANCE@clinic.ub.es.
authors.forename: A M
authors.initials: AM
authors.lastname: Arance
authors.affiliation: Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Berrocal
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Lopez-Martin
authors.affiliation: Hospital Univ. Virgen de la Macarena de Sevilla, Seville, Spain.
authors.forename: L
authors.initials: L
authors.lastname: de la Cruz-Merino
authors.affiliation: Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Soriano
authors.affiliation: Clínica Universidad de Navarra, Navarra, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Martín Algarra
authors.affiliation: Hospital Clínico de Málaga, Malaga, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Alonso
authors.affiliation: Hospital Universitario Santa Lucía de Cartagena, Cartagena, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Cerezuela
authors.affiliation: Roche Farma, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: La Orden
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Espinosa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics; D013030:Spain; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Melanoma; Safety study; Spain; Vemurafenib