Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAF(V600) mutation-positive metastatic melanoma
| Autor: | Christian U. Blank, Jacob Schachter, Claus Garbe, Paola Queirolo, Geke A. P. Hospers, Vanna Chiarion Sileni, Helen Gogas, Michael P. Brown, Bart Neyns, Ana Arance, Martina Makrutzki, Enrique Espinosa, Michele Del Vecchio, Vladan Antic, James E. Larkin, Wilson H. Miller, Ivana Krajsová, Mario Mandalà, Susan Robson, Axel Hauschild, Paolo A. Ascierto |
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| Přispěvatelé: | Blank, Christian U, Larkin, James, Arance, Ana M, Hauschild, Axel, Brown, Michael Paul, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Oncology
safety Cancer Research medicine.medical_specialty Keratoacanthoma PHASE-3 Population Ipilimumab Metastatic melanoma TRAMETINIB BRAF 03 medical and health sciences chemistry.chemical_compound DOUBLE-BLIND 0302 clinical medicine Internal medicine Medicine BRAF(V600) mutation 030212 general & internal medicine Vemurafenib education Trametinib Cobimetinib education.field_of_study business.industry Melanoma IPILIMUMAB Dabrafenib RANDOMIZED CONTROLLED-TRIAL COBIMETINIB medicine.disease EFFICACY Dermatology DABRAFENIB chemistry BRAFV600 mutation 030220 oncology & carcinogenesis SURVIVAL Safety business medicine.drug metastatic melanoma |
| Zdroj: | European Journal of Cancer, 79, 176-184. ELSEVIER SCI LTD |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2017.04.007 |
| Popis: | Background: The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF(V600) 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 (R) 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 BRAF(V600) mutation-positive metastatic melanoma who are more representative of routine clinical practice than typical clinical trial populations. These data suggest that longterm vemurafenib treatment is effective and tolerable without the development of new safety signals. (C) 2017 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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