TY - JOUR
T1 - Vemurafenib in patients with BRAFV600 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 - Mandalà, 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.
N1 - Funding Information:
JL has received research funding from Pfizer and Novartis and has been a consultant or participated in advisory boards for Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, and Novartis; and is supported by the Royal Marsden and Institute of Cancer Research NIHR Biomedical Research Centre for Cancer. MDV has been an adviser for Merck, Sharp, and Dohme, and Schering-Plough; received honoraria from Roche, Celgene, and GlaxoSmithKline; and received research funding from Roche, Celgene, GlaxoSmithKline, and Bristol-Myers Squibb. PAA has received research funding from Bristol-Myers Squibb and has been a consultant or participated on advisory boards for Bristol-Myers Squibb, Roche-Genentech, GlaxoSmithKline, and Novartis. JS has received honoraria as a speaker and member of a steering committee for Roche. CG has received honoraria from F Hoffmann-La Roche for presentations and advisory activities, and received research grants from F Hoffmann-La Roche. VC-S has received compensation for participation in advisory boards from Bristol-Myers Squibb, Roche-Genentech, and GlaxoSmithKline. WHM has received paid consultant agreements and travel grants from Roche and Bristol-Myers Squibb. MM has participated in advisory boards for Roche-Genentech, GlaxoSmithKline, and Bristol-Myers Squibb. AA has received funding for board membership, lectures, and travel expenses from Roche and Bristol-Myers Squibb. PQ has served on advisory boards for Roche, GlaxoSmithKline, and Bristol-Myers Squibb. AH has received honoraria for advisory board membership and consultancy and has received payment for lectures, including services on speaker bureaus and research funding from the following companies: Amgen, 8MS, Celgene, Eisai, GlaxoSmithKline, MedImmune, MelaSciences, Merck Serono, Merck, Sharp, and Dohme, Merck, Novartis, Oncosec, and Roche Pharma. MB has received honoraria for advisory board involvement for Roche Products Australia and travel expenses for steering committee meetings for this study, paid for by Roche. LM and LV are employees of F Hoffmann-La Roche. CB has received research funding from Novartis and MedImmune and has been a consultant or participated in advisory boards for Roche, Merck, Sharp, and Dohme, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. The other authors declare that they have no competing interests.
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 BRAFV600 mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAFV600 mutations who had few treatment options. Methods: In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAFV600 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 BRAFV600 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. Funding: F Hoffmann-La Roche.
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 BRAFV600 mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAFV600 mutations who had few treatment options. Methods: In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAFV600 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 BRAFV600 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. Funding: F Hoffmann-La Roche.
UR - http://www.scopus.com/inward/record.url?scp=84897458716&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(14)70051-8
DO - 10.1016/S1470-2045(14)70051-8
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C2 - 24582505
AN - SCOPUS:84897458716
SN - 1470-2045
VL - 15
SP - 436
EP - 444
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 4
ER -
