Journal article
Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long-term responders' analysis.
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Blank CU
The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, The Netherlands. Electronic address: c.blank@nki.nl.
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Larkin J
The Royal Marsden NHS Foundation Trust, London, UK. Electronic address: James.Larkin@rmh.nhs.uk.
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Arance AM
Department of Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain. Electronic address: AMARANCE@clinic.ub.es.
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Hauschild A
Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany. Electronic address: ahauschild@dermatology.uni-kiel.de.
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Queirolo P
IRCCS San Martino-IST, Genova, Italy. Electronic address: paola.queirolo@hsanmartino.it.
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Del Vecchio M
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Michele.delvecchio@istitutotumori.mi.it.
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Ascierto PA
Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. Electronic address: paolo.ascierto@gmail.com.
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Krajsova I
General University Hospital, Dermatooncology U, Prague, Czech Republic. Electronic address: Ivana.Krajsova@vfn.cz.
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Schachter J
Chaim Sheba Medical Centre, Oncology Institute, Ramat-Gan, Israel. Electronic address: Jacob.schachter@sheba.health.gov.il.
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Neyns B
Afdelingshoofd, Medische Oncologie, Brussels, Belgium. Electronic address: bart.neyns@uzbrussel.be.
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Garbe C
Department of Dermatology, University Hospital Tuebingen, Tuebingen, Germany. Electronic address: claus.garbe@med.uni-tuebingen.de.
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Chiarion Sileni V
Oncology Institute of Veneto-IRCCS, Padova, Italy. Electronic address: vanna.chiarion@ioveneto.it.
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Mandalà M
Papa Giovanni XIII Hospital, Bergamo, Italy. Electronic address: mariomandala@tin.it.
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Gogas H
University of Athens, Athens, Greece. Electronic address: hgogas@hol.gr.
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Espinosa E
Hospital La Paz, Madrid, Spain. Electronic address: eespinosa00@hotmail.com.
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Hospers GAP
University Medical Centre Groningen, Groningen, The Netherlands. Electronic address: g.a.p.hospers@umcg.nl.
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Miller WH
McGill University, Segal Cancer Centre, Montreal, Quebec, Canada. Electronic address: wilsonmiller@gmail.com.
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Robson S
F. Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: susan.robson@roche.com.
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Makrutzki M
F. Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: martina.makrutzki@roche.com.
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Antic V
F. Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: vladan.antic@roche.com.
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Brown MP
Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, Australia; Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia; Discipline of Medicine, University of Adelaide, Adelaide, Australia. Electronic address: MichaelP.brown@sa.gov.au.
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Published in:
- European journal of cancer (Oxford, England : 1990). - 2017
English
BACKGROUND
The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAFV600 mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety.
METHODS
This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas® 4800 BRAF V600 Mutation Test). The primary end-point was safety; efficacy end-points were secondary. An exploratory analysis was performed to assess safety outcomes in patients with long duration of response (DOR) (≥12 or ≥24 months).
RESULTS
After a median follow-up of 32.2 months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued treatment. Adverse events (AEs) were largely consistent with previous reports; the most common all-grade treatment-related AEs were arthralgia (37%), alopecia (25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the exploratory analysis, patients with DOR ≥12 months (n = 287) or ≥24 months (n = 133) were more likely to experience grade 3/4 AEs than the overall population. No new specific safety signals were observed with longer vemurafenib exposure.
CONCLUSIONS
After 2 years' follow-up, safety was maintained in this large group of patients with BRAFV600 mutation-positive metastatic melanoma who are more representative of routine clinical practice than typical clinical trial populations. These data suggest that long-term vemurafenib treatment is effective and tolerable without the development of new safety signals.
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Language
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Open access status
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closed
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/39608
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