TY - JOUR
TI - An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma: final analysis and a validated prognostic scoring system
AU - Larkin, J.
AU - Brown, M.P.
AU - Arance, A.M.
AU - Hauschild, A.
AU - Queirolo, P.
AU - Vecchio, M.D.
AU - Ascierto, P.A.
AU - Krajsová, I.
AU - Schachter, J.
AU - Neyns, B.
AU - Garbe, C.
AU - Sileni, V.C.
AU - Mandalà, M.
AU - Gogas, H.
AU - Espinosa, E.
AU - Hospers, G.
AU - Lorigan, P.
AU - Nyakas, M.
AU - Guminski, A.
AU - Liszkay, G.
AU - Rutkowski, P.
AU - Miller, W., Jr.
AU - Donica, M.
AU - Makrutzki, M.
AU - Blank, C.
JO - EUROPEAN JOURNAL OF CANCER
PY - 2019
VL - 107
TODO - null
SP - 175-185
PB - Elsevier Ireland Ltd
SN - null
TODO - 10.1016/j.ejca.2018.11.018
TODO - B Raf kinase;  cobimetinib;  dacarbazine;  lactate dehydrogenase;  vemurafenib;  antineoplastic agent;  B Raf kinase;  BRAF protein, human;  vemurafenib, abdominal bleeding;  abdominal pain;  actinic keratosis;  acute heart infarction;  aged;  alopecia;  anemia;  arthralgia;  Article;  asthenia;  backache;  basal cell carcinoma;  body weight disorder;  body weight loss;  brain hematoma;  brain hemorrhage;  brain metastasis;  cancer chemotherapy;  cancer patient;  cancer prognosis;  cancer survival;  cardiogenic shock;  chronic fatigue syndrome;  conjunctivitis;  constipation;  controlled study;  coughing;  decreased appetite;  diarrhea;  disease exacerbation;  disseminated intravascular clotting;  drug safety;  dry skin;  dysgeusia;  dyspnea;  erythema;  fatigue;  fever;  follow up;  general condition deterioration;  hand foot syndrome;  headache;  human;  hyperkeratosis;  hypertension;  insomnia;  keratoacanthoma;  lactate dehydrogenase blood level;  limb pain;  lung toxicity;  major clinical study;  metastatic melanoma;  multicenter study;  multiple organ failure;  musculoskeletal pain;  myalgia;  nausea;  open study;  overall survival;  peripheral edema;  photosensitivity;  pigmented nevus;  pneumonia;  primary tumor;  priority journal;  pruritus;  QT prolongation;  rash;  rhinopharyngitis;  sepsis;  skin papilloma;  spleen metastasis;  squamous cell carcinoma;  squamous cell skin carcinoma;  sunburn;  torsade des pointes;  unspecified side effect;  vomiting;  brain tumor;  clinical trial;  female;  genetics;  lymph node metastasis;  male;  melanoma;  mutation;  nomogram;  pathology;  prognosis;  survival rate;  validation study, Aged;  Antineoplastic Agents;  Brain Neoplasms;  Female;  Follow-Up Studies;  Humans;  Lymphatic Metastasis;  Male;  Melanoma;  Mutation;  Nomograms;  Prognosis;  Proto-Oncogene Proteins B-raf;  Survival Rate;  Validation Studies as Topic;  Vemurafenib
TODO - Background: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. Patients and methods: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). Results: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. Conclusions: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work. © 2018 Elsevier Ltd
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