Vemurafenib in patients with BRAFV600 mutated metastatic melanoma

An open-label, multicentre, safety study

James Larkin, Michele Del Vecchio, Paolo A. Ascierto, Ivana Krajsova, Jacob Schachter, Bart Neyns, Enrique Espinosa, Claus Garbe, Vanna Chiarion Sileni, Helen Gogas, Wilson H. Miller, Mario Mandalà, Geke A P Hospers, Ana Arance, Paola Queirolo, Axel Hauschild, Michael P. Brown, Lada Mitchell, Luisa Veronese, Christian U. Blank

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

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 At data cutoff, 868 (27%) patients were on study treatment and 2354 (73%) had withdrawn, mainly because of disease progression.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.

Original languageEnglish
Pages (from-to)436-444
Number of pages9
JournalThe Lancet Oncology
Volume15
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Multicenter Studies
Melanoma
Safety
Arthralgia
Exanthema
Mutation
Fatigue
Proto-Oncogene Proteins B-raf
PLX4032
Population
Dacarbazine
Alopecia
Nausea
Disease-Free Survival
Disease Progression
Squamous Cell Carcinoma
Skin
Survival
Liver
Therapeutics

ASJC Scopus subject areas

  • Oncology

Cite this

Vemurafenib in patients with BRAFV600 mutated metastatic melanoma : An open-label, multicentre, safety study. / Larkin, James; Del Vecchio, Michele; Ascierto, Paolo A.; Krajsova, Ivana; Schachter, Jacob; Neyns, Bart; Espinosa, Enrique; Garbe, Claus; Sileni, Vanna Chiarion; Gogas, Helen; Miller, Wilson H.; Mandalà, Mario; Hospers, Geke A P; Arance, Ana; Queirolo, Paola; Hauschild, Axel; Brown, Michael P.; Mitchell, Lada; Veronese, Luisa; Blank, Christian U.

In: The Lancet Oncology, Vol. 15, No. 4, 2014, p. 436-444.

Research output: Contribution to journalArticle

Larkin, J, Del Vecchio, M, Ascierto, PA, Krajsova, I, Schachter, J, Neyns, B, Espinosa, E, Garbe, C, Sileni, VC, Gogas, H, Miller, WH, Mandalà, M, Hospers, GAP, Arance, A, Queirolo, P, Hauschild, A, Brown, MP, Mitchell, L, Veronese, L & Blank, CU 2014, 'Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: An open-label, multicentre, safety study', The Lancet Oncology, vol. 15, no. 4, pp. 436-444. https://doi.org/10.1016/S1470-2045(14)70051-8
Larkin, James ; Del Vecchio, Michele ; Ascierto, Paolo A. ; Krajsova, Ivana ; Schachter, Jacob ; Neyns, Bart ; Espinosa, Enrique ; Garbe, Claus ; Sileni, Vanna Chiarion ; Gogas, Helen ; Miller, Wilson H. ; Mandalà, Mario ; Hospers, Geke A P ; Arance, Ana ; Queirolo, Paola ; Hauschild, Axel ; Brown, Michael P. ; Mitchell, Lada ; Veronese, Luisa ; Blank, Christian U. / Vemurafenib in patients with BRAFV600 mutated metastatic melanoma : An open-label, multicentre, safety study. In: The Lancet Oncology. 2014 ; Vol. 15, No. 4. pp. 436-444.
@article{9064f646f0e748c49960d54a01d01075,
title = "Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: An open-label, multicentre, safety study",
abstract = "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.",
author = "James Larkin and {Del Vecchio}, Michele and Ascierto, {Paolo A.} and Ivana Krajsova and Jacob Schachter and Bart Neyns and Enrique Espinosa and Claus Garbe and Sileni, {Vanna Chiarion} and Helen Gogas and Miller, {Wilson H.} and Mario Mandal{\`a} and Hospers, {Geke A P} and Ana Arance and Paola Queirolo and Axel Hauschild and Brown, {Michael P.} and Lada Mitchell and Luisa Veronese and Blank, {Christian U.}",
year = "2014",
doi = "10.1016/S1470-2045(14)70051-8",
language = "English",
volume = "15",
pages = "436--444",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "4",

}

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.

PY - 2014

Y1 - 2014

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

UR - http://www.scopus.com/inward/citedby.url?scp=84897458716&partnerID=8YFLogxK

U2 - 10.1016/S1470-2045(14)70051-8

DO - 10.1016/S1470-2045(14)70051-8

M3 - Article

VL - 15

SP - 436

EP - 444

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 4

ER -