A comparative study of the cutaneous side effects between BRAF monotherapy and BRAF/MEK inhibitor combination therapy in patients with advanced melanoma: a single-centre experience

被引:9
作者
Russo, Irene [1 ]
Zorzetto, Ludovica [1 ]
Frigo, Anna Chiara [2 ]
Sileni, Vanna Chiarion [3 ]
Alaibac, Mauro [1 ]
机构
[1] Univ Padua, Unit Dermatol, Via Gallucci 4, I-35128 Padua, Italy
[2] Univ Padua, Unit Biostat Epidemiol & Publ Hlth, Dept Cardiac Thorac & Vasc Sci, Via Loredan 18, I-35131 Padua, Italy
[3] Veneto Inst Oncol IOV IRCCS, Med Oncol Unit, I-35128 Padua, Italy
关键词
BRAF inhibitor; cutaneous side effect; MEK inhibitor; melanoma; SQUAMOUS-CELL CARCINOMAS; MUTATED METASTATIC MELANOMA; OPEN-LABEL; IMPROVED SURVIVAL; MEK INHIBITION; RAS MUTATIONS; VEMURAFENIB; DABRAFENIB; TOXICITIES; MULTICENTER;
D O I
10.1684/ejd.2017.3069
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background: Patients with advanced melanoma have a poor prognosis. Since the discovery of BRAF mutations in cutaneous melanoma, new pharmacological agents have been developed to inhibit this target. Although the survival of patients with advanced melanoma has improved with BRAF inhibitors, the emergence of drug resistance and the high incidence of cutaneous side effects represent important limitations. Objectives: The aim of our study was to compare the incidence of cutaneous side effects between BRAF inhibitor monotherapy and BRAF and MEK inhibitor combination therapy in our cohort of patients. Materials & methods: This study was a longitudinal prospective observational study. The study population comprised 83 patients with advanced cutaneous melanoma presenting with BRAF V600 mutation. The inclusion criteria included: age above 18 years, metastatic cutaneous melanoma or melanoma with high risk of metastasis, the presence of BRAF V600 mutation, and treatment with BRAFinhibitors or a combination of BRAF and MEK inhibitors. Results: The majority of patients developed skin toxicity during treatment. The most common cutaneous side effects were localized hyperkeratosis and verrucous keratosis. Other cutaneous side effects observed were photosensitivity, squamous cell carcinoma, and keratoacanthoma. Conclusion: Our results indicate that cutaneous side effects are generally observed during BRAF inhibitor monotherapy and are significantly different from those observed in patients treated with combination therapy.
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收藏
页码:482 / 486
页数:5
相关论文
共 33 条
[1]   Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma [J].
Anforth, R. M. ;
Blumetti, T. C. M. P. ;
Kefford, R. F. ;
Sharma, R. ;
Scolyer, R. A. ;
Kossard, S. ;
Long, G. V. ;
Fernandez-Penas, P. .
BRITISH JOURNAL OF DERMATOLOGY, 2012, 167 (05) :1153-1160
[2]   Cutaneous toxicities of RAF inhibitors [J].
Anforth, Rachael ;
Fernandez-Penas, Pablo ;
Long, Georgina V. .
LANCET ONCOLOGY, 2013, 14 (01) :E11-E18
[3]   Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors [J].
Anforth, Rachael ;
Tembe, Varsha ;
Blumetti, Tatiana ;
Fernandez-Penas, Pablo .
PIGMENT CELL & MELANOMA RESEARCH, 2012, 25 (05) :569-572
[4]   The role of BRAF V600 mutation in melanoma [J].
Ascierto, Paolo A. ;
Kirkwood, John M. ;
Grob, Jean-Jacques ;
Simeone, Ester ;
Grimaldi, Antonio M. ;
Maio, Michele ;
Palmieri, Giuseppe ;
Testori, Alessandro ;
Marincola, Francesco M. ;
Mozzillo, Nicola .
JOURNAL OF TRANSLATIONAL MEDICINE, 2012, 10
[5]   Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors forMetastatic Melanoma [J].
Carlos, Giuliana ;
Anforth, Rachael ;
Clements, Arthur ;
Menzies, Alexander M. ;
Carlino, Matteo S. ;
Chou, Shaun ;
Fernandez-Penas, Pablo .
JAMA DERMATOLOGY, 2015, 151 (10) :1103-1109
[6]   Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation [J].
Chapman, Paul B. ;
Hauschild, Axel ;
Robert, Caroline ;
Haanen, John B. ;
Ascierto, Paolo ;
Larkin, James ;
Dummer, Reinhard ;
Garbe, Claus ;
Testori, Alessandro ;
Maio, Michele ;
Hogg, David ;
Lorigan, Paul ;
Lebbe, Celeste ;
Jouary, Thomas ;
Schadendorf, Dirk ;
Ribas, Antoni ;
O'Day, Steven J. ;
Sosman, Jeffrey A. ;
Kirkwood, John M. ;
Eggermont, Alexander M. M. ;
Dreno, Brigitte ;
Nolop, Keith ;
Li, Jiang ;
Nelson, Betty ;
Hou, Jeannie ;
Lee, Richard J. ;
Flaherty, Keith T. ;
McArthur, Grant A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (26) :2507-2516
[7]   Mutations of the BRAF gene in human cancer [J].
Davies, H ;
Bignell, GR ;
Cox, C ;
Stephens, P ;
Edkins, S ;
Clegg, S ;
Teague, J ;
Woffendin, H ;
Garnett, MJ ;
Bottomley, W ;
Davis, N ;
Dicks, N ;
Ewing, R ;
Floyd, Y ;
Gray, K ;
Hall, S ;
Hawes, R ;
Hughes, J ;
Kosmidou, V ;
Menzies, A ;
Mould, C ;
Parker, A ;
Stevens, C ;
Watt, S ;
Hooper, S ;
Wilson, R ;
Jayatilake, H ;
Gusterson, BA ;
Cooper, C ;
Shipley, J ;
Hargrave, D ;
Pritchard-Jones, K ;
Maitland, N ;
Chenevix-Trench, G ;
Riggins, GJ ;
Bigner, DD ;
Palmieri, G ;
Cossu, A ;
Flanagan, A ;
Nicholson, A ;
Ho, JWC ;
Leung, SY ;
Yuen, ST ;
Weber, BL ;
Siegler, HF ;
Darrow, TL ;
Paterson, H ;
Marais, R ;
Marshall, CJ ;
Wooster, R .
NATURE, 2002, 417 (6892) :949-954
[8]   BRAF Signaling and Targeted Therapies in Melanoma [J].
Dhomen, Nathalie ;
Marais, Richard .
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 2009, 23 (03) :529-+
[9]  
Fava P, 2016, GIORN ITAL DERMAT V, V151, P25
[10]   Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma [J].
Flaherty, Keith T. ;
Robert, Caroline ;
Hersey, Peter ;
Nathan, Paul ;
Garbe, Claus ;
Milhem, Mohammed ;
Demidov, Lev V. ;
Hassel, Jessica C. ;
Rutkowski, Piotr ;
Mohr, Peter ;
Dummer, Reinhard ;
Trefzer, Uwe ;
Larkin, James M. G. ;
Utikal, Jochen ;
Dreno, Brigitte ;
Nyakas, Marta ;
Middleton, Mark R. ;
Becker, Juergen C. ;
Casey, Michelle ;
Sherman, Laurie J. ;
Wu, Frank S. ;
Ouellet, Daniele ;
Martin, Anne-Marie ;
Patel, Kiran ;
Schadendorf, Dirk .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (02) :107-114