High BRAF V600 Mutation Level Associated with Worse Outcome in Metastatic Melanoma Patients Receiving BRAF and MEK Inhibitors

被引:0
作者
Fizazi, Ariane [1 ]
Serrand, Chris [2 ]
Evrard, Alexandre [3 ,4 ]
Bergeret, Blanche [1 ]
Stoebner, Pierre-Emmanuel [1 ]
Marque, Myriam [1 ]
机构
[1] Univ Montpellier, CHU Nimes, Dept Dermatol, FR-30029 Nimes, France
[2] Univ Montpellier, CHU Nimes, Dept Biostat Epidemiol Publ Hlth & Innovat Methodo, Nimes, France
[3] Univ Montpellier, CHU Nimes, Lab Biochem & Mol Biol, Montpellier, France
[4] Univ Montpellier, Inst Rech Cancerol Montpellier IRCM, Inst Reg Canc Montpellier ICM, INSERM U1194, Montpellier, France
关键词
melanoma; BRAF V600; MAPKi; biomarker;
D O I
10.2340/actadv.v104.40913
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
The prognostic value of BRAF V600 mutation level on clinical outcomes in patients with BRAF V600-mutated metastatic melanoma treated with BRAF and MEK inhibitors remains uncertain. The association was retrospectively analysed between BRAF V600 mutation level (defined as the ratio of the quantification of the BRAF V600 allele to the percentage of tumoral cells in the sample analysed) and progression-free and overall survival (PFS and OS, respectively) and 3-month response rate in a cohort of 58 patients with metastatic melanoma who harboured BRAF V600E/K mutations and received dual targeted-therapy BRAF/MEK inhibitors. The BRAF mutation level cut-off determined by the area under the receiver operating characteristic curve after internal validation by bootstrap methods was 0.44. Risk of poor PFS and OS was associated with BRAF V600 mutation level > 0.44 on multivariate analysis (p = 0.02 and p = 0.02, respectively) after adjusting for major confounding factors (age, sex, lactate dehydrogenase level, brain metastasis, and treatment line). No association was found between BRAF mutation level and 3-month response rate. Our study shows that high BRAF V600 mutation level in melanoma tissue was associated with poor prognosis in patients with metastatic melanoma treated with BRAF and MEK inhibitors.
引用
收藏
页数:5
相关论文
共 15 条
  • [1] Clinical and therapeutic implications of BRAF mutation heterogeneity in metastatic melanoma
    Ardakani, Nima Mesbah
    Leslie, Connull
    Grieu-Iacopetta, Fabienne
    Lam, Wei-Sen
    Budgeon, Charley
    Millward, Michael
    Amanuel, Benhur
    [J]. PIGMENT CELL & MELANOMA RESEARCH, 2017, 30 (02) : 233 - 242
  • [2] Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial
    Ascierto, Paolo A.
    Casula, Milena
    Bulgarelli, Jenny
    Pisano, Marina
    Piccinini, Claudia
    Piccin, Luisa
    Cossu, Antonio
    Mandala, Mario
    Ferrucci, Pier Francesco
    Guidoboni, Massimo
    Rutkowski, Piotr
    Ferraresi, Virginia
    Arance, Ana
    Guida, Michele
    Maiello, Evaristo
    Gogas, Helen
    Richtig, Erika
    Fierro, Maria Teresa
    Lebbe, Celeste
    Helgadottir, Hildur
    Queirolo, Paola
    Spagnolo, Francesco
    Tucci, Marco
    Del Vecchio, Michele
    Cao, Maria Gonzales
    Minisini, Alessandro Marco
    De Placido, Sabino
    Sanmamed, Miguel F.
    Mallardo, Domenico
    Paone, Miriam
    Vitale, Maria Grazia
    Melero, Ignacio
    Grimaldi, Antonio M.
    Giannarelli, Diana
    Dummer, Reinhard
    Sileni, Vanna Chiarion
    Palmieri, Giuseppe
    [J]. NATURE COMMUNICATIONS, 2024, 15 (01)
  • [3] High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients
    Berrino, E.
    Balsamo, A.
    Pisacane, A.
    Gallo, S.
    Becco, P.
    Miglio, U.
    Caravelli, D.
    Poletto, S.
    Paruzzo, L.
    Debernardi, C.
    Piccinelli, C.
    Zaccagna, A.
    Rescigno, P.
    Aglietta, M.
    Sapino, A.
    Carnevale-Schianca, F.
    Venesio, T.
    [J]. ESMO OPEN, 2021, 6 (03)
  • [4] Comparison of BRAF Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients
    Colombino, Maria
    Rozzo, Carla
    Paliogiannis, Panagiotis
    Casula, Milena
    Manca, Antonella
    Doneddu, Valentina
    Fedeli, Maria Antonietta
    Sini, Maria Cristina
    Palomba, Grazia
    Pisano, Marina
    Ascierto, Paolo A.
    Caraco, Corrado
    Lissia, Amelia
    Cossu, Antonio
    Palmieri, Giuseppe
    [J]. JOURNAL OF CLINICAL MEDICINE, 2020, 9 (08) : 1 - 14
  • [5] BRAFV600 mutation levels predict response to vemurafenib in metastatic melanoma
    Lebbe, Celeste
    How-Kit, Alexandre
    Battistella, Maxime
    Sadoux, Aurelie
    Podgorniak, Marie-Pierre
    Sidina, Irina
    Pages, Cecile
    Roux, Jennifer
    Porcher, Raphael
    Tost, Jorg
    Mourah, Samia
    [J]. MELANOMA RESEARCH, 2014, 24 (04) : 415 - 418
  • [6] BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors
    Mandala, Mario
    Palmieri, Giuseppe
    Ludovini, Vienna
    Baglivo, Sara
    Marasciulo, Francesca
    Castiglione, Francesca
    Gili, Alessio
    Abate, Simona Osella
    Rubatto, Marco
    Senetta, Rebecca
    Avallone, Gianluca
    Ribero, Simone
    Romano, Luca
    Pimpinelli, Nicola
    de Giorgi, Vincenzo
    Roila, Fausto
    Pisano, Marina
    Casula, Milena
    Manca, Antonella
    Sini, Maria Cristina
    Massi, Daniela
    Quaglino, Pietro
    [J]. JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2023, 37 (10) : 1991 - 1998
  • [7] Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma
    Robert, C.
    Grob, J. J.
    Stroyakovskiy, D.
    Karaszewska, B.
    Hauschild, A.
    Levchenko, E.
    Sileni, V. Chiarion
    Schachter, J.
    Garbe, C.
    Bondarenko, I.
    Gogas, H.
    Mandala, M.
    Haanen, J. B. A. G.
    Lebbe, C.
    Mackiewicz, A.
    Rutkowski, P.
    Nathan, P. D.
    Ribas, A.
    Davies, M. A.
    Flaherty, K. T.
    Burgess, P.
    Tan, M.
    Gasal, E.
    Voi, M.
    Schadendorf, D.
    Long, G. V.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2019, 381 (07) : 626 - 636
  • [8] Allele frequencies of BRAFV600 mutations in primary melanomas and matched metastases and their relevance for BRAF inhibitor therapy in metastatic melanoma
    Satzger, Imke
    Marks, Lena
    Kerick, Martin
    Klages, Sven
    Berking, Carola
    Herbst, Rudolf
    Voelker, Bernward
    Schacht, Vivien
    Timmermann, Bernd
    Gutzmer, Ralf
    [J]. ONCOTARGET, 2015, 6 (35) : 37895 - 37905
  • [9] Long-Term Outcomes in BRAF-Mutated Melanoma Treated with Combined Targeted Therapy or Immune Checkpoint Blockade: Are We Approaching a True Cure?
    Schummer, Patrick
    Schilling, Bastian
    Gesierich, Anja
    [J]. AMERICAN JOURNAL OF CLINICAL DERMATOLOGY, 2020, 21 (04) : 493 - 504
  • [10] Systemic Therapy for Melanoma: ASCO Guideline Update
    Seth, Rahul
    Agarwala, Sanjiv S.
    Messersmith, Hans
    Alluri, Krishna C.
    Ascierto, Paolo A.
    Atkins, Michael B.
    Bollin, Kathryn
    Chacon, Matias
    Davis, Nancy
    Faries, Mark B.
    Funchain, Pauline
    Gold, Jason S.
    Guild, Samantha
    Gyorki, David E.
    Kaur, Varinder
    Khushalani, Nikhil I.
    Kirkwood, John M.
    McQuade, Jennifer Leigh
    Meyers, Michael O.
    Provenzano, Anthony
    Robert, Caroline
    Santinami, Mario
    Sehdev, Amikar
    Sondak, Vernon K.
    Spurrier, Gilliosa
    Swami, Umang
    Truong, Thach-Giao
    Tsai, Katy K.
    van Akkooi, Alexander
    Weber, Jeffrey
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (30) : 4794 - +