TY - JOUR
T1 - Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma
T2 - An open-label, multicentre, safety study
AU - Larkin, James
AU - Del Vecchio, Michele
AU - Ascierto, Paolo A.
AU - Krajsova, Ivana
AU - Schachter, Jacob
AU - Neyns, Bart
AU - Espinosa, Enrique
AU - Garbe, Claus
AU - Sileni, Vanna Chiarion
AU - Gogas, Helen
AU - Miller, Wilson H.
AU - Mandala, Mario
AU - Hospers, Geke A. P.
AU - Arance, Ana
AU - Queirolo, Paola
AU - Hauschild, Axel
AU - Brown, Michael P.
AU - Mitchell, Lada
AU - Veronese, Luisa
AU - Blank, Christian U.
PY - 2014/4
Y1 - 2014/4
N2 - Background The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved response rates, progression- free survival (PFS), and overall survival in patients with metastatic melanoma that has a BRAF(V600) mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAF(V600) mutations who had few treatment options.Methods In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day. The primary endpoint was safety. All analyses were done on the safety population, which included all patients who received at least one dose of vemurafenib. This report is the third interim analysis of this study. This study is registered with ClinicalTrials.gov, number NCT01307397.Findings Between March 1, 2011, and Jan 31, 2013, 3226 patients were enrolled in 44 countries. 3222 patients received at least one dose of vemurafenib (safety population). At data cutoff, 868 (27%) patients were on study treatment and 2354 (73%) had withdrawn, mainly because of disease progression. Common adverse events of all grades included rash (1592 [49%]), arthralgia (1259 [39%]), fatigue (1093 [34%]), photosensitivity reaction (994 [31%]), alopecia (826 [26%]), and nausea (628 [19%]). 1480 (46%) patients reported grade 3 or 4 adverse events, including cutaneous squamous cell carcinoma (389 [12%]), rash (155 [5%]), liver function abnormalities (165 [5%]), arthralgia (106 [3%]), and fatigue (93 [3%]). Grade 3 and 4 adverse events were reported more frequently in patients aged 75 years and older (n= 257; 152 [59%, 95% CI 53- 65] and ten [4%, 2- 7], respectively) than in those younger than 75 years (n= 2965; 1286 [43%, 42- 45] and 82 [3%, 2- 3], respectively).Interpretation Vemurafenib safety in this diverse population of patients with BRAF(V600) mutated metastatic melanoma, who are more representative of routine clinical practice, was consistent with the safety profile shown in the pivotal trials of this drug.
AB - Background The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved response rates, progression- free survival (PFS), and overall survival in patients with metastatic melanoma that has a BRAF(V600) mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAF(V600) mutations who had few treatment options.Methods In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day. The primary endpoint was safety. All analyses were done on the safety population, which included all patients who received at least one dose of vemurafenib. This report is the third interim analysis of this study. This study is registered with ClinicalTrials.gov, number NCT01307397.Findings Between March 1, 2011, and Jan 31, 2013, 3226 patients were enrolled in 44 countries. 3222 patients received at least one dose of vemurafenib (safety population). At data cutoff, 868 (27%) patients were on study treatment and 2354 (73%) had withdrawn, mainly because of disease progression. Common adverse events of all grades included rash (1592 [49%]), arthralgia (1259 [39%]), fatigue (1093 [34%]), photosensitivity reaction (994 [31%]), alopecia (826 [26%]), and nausea (628 [19%]). 1480 (46%) patients reported grade 3 or 4 adverse events, including cutaneous squamous cell carcinoma (389 [12%]), rash (155 [5%]), liver function abnormalities (165 [5%]), arthralgia (106 [3%]), and fatigue (93 [3%]). Grade 3 and 4 adverse events were reported more frequently in patients aged 75 years and older (n= 257; 152 [59%, 95% CI 53- 65] and ten [4%, 2- 7], respectively) than in those younger than 75 years (n= 2965; 1286 [43%, 42- 45] and 82 [3%, 2- 3], respectively).Interpretation Vemurafenib safety in this diverse population of patients with BRAF(V600) mutated metastatic melanoma, who are more representative of routine clinical practice, was consistent with the safety profile shown in the pivotal trials of this drug.
KW - MALIGNANT-MELANOMA
KW - BRAIN METASTASES
KW - SURVIVAL
KW - PROGRESSION
U2 - 10.1016/S1470-2045(14)70051-8
DO - 10.1016/S1470-2045(14)70051-8
M3 - Article
SN - 1470-2045
VL - 15
SP - 436
EP - 444
JO - Lancet Oncology
JF - Lancet Oncology
IS - 4
ER -