Journal Article

DKFZ-2019-02337

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Targeted Therapy in Advanced Melanoma With Rare BRAF Mutations.

Menzer, C. ; Menzies, A. M. ; Carlino, M. S. ; Reijers, I. ; Groen, E. J. ; Eigentler, T. ; de Groot, J. W. B. ; van der Veldt, A. A. M. ; Johnson, D. B. ; Meiss, F. ; Schlaak, M. ; Schilling, B. ; Westgeest, H. M. ; Gutzmer, R. ; Pföhler, C. ; Meier, F. ; Zimmer, L. ; Suijkerbuijk, K. P. M. ; Haalck, T. ; Thoms, K.-M. ; Herbschleb, K. ; Leichsenring, J. ; Menzer, A. ; Kopp-Schneider, A.DKFZ* ; Long, G. V. ; Kefford, R. ; Enk, A. ; Blank, C. U. ; Hassel, J. C.

2019
American Society of Clinical Oncology Alexandria, Va.

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Please use a persistent id in citations: doi:10.1200/JCO.19.00489

Abstract: BRAF/MEK inhibition is a standard of care for patients with BRAF V600E/K-mutated metastatic melanoma. For patients with less frequent BRAF mutations, however, efficacy data are limited.In the current study, 103 patients with metastatic melanoma with rare, activating non-V600E/K BRAF mutations that were treated with either a BRAF inhibitor (BRAFi), MEK inhibitor (MEKi), or the combination were included. BRAF mutation, patient and disease characteristics, response, and survival data were analyzed.Fifty-eight patient tumors (56%) harbored a non-E/K V600 mutation, 38 (37%) a non-V600 mutation, and seven had both V600E and a rare BRAF mutation (7%). The most frequent mutations were V600R (43%; 44 of 103), L597P/Q/R/S (15%; 15 of 103), and K601E (11%; 11 of 103). Most patients had stage IV disease and 42% had elevated lactate dehydrogenase at BRAFi/MEKi initiation. Most patients received combined BRAFi/MEKi (58%) or BRAFi monotherapy (37%). Of the 58 patients with V600 mutations, overall response rate to BRAFi monotherapy and combination BRAFi/MEKi was 27% (six of 22) and 56% (20 of 36), respectively, whereas median progression-free survival (PFS) was 3.7 months and 8.0 months, respectively (P = .002). Of the 38 patients with non-V600 mutations, overall response rate was 0% (zero of 15) to BRAFi, 40% (two of five) to MEKi, and 28% (five of 18) to combination treatment, with a median PFS of 1.8 months versus 3.7 months versus 3.3 months, respectively. Multivariable analyses revealed superior survival (PFS and overall survival) with combination over monotherapy in rare V600 and non-V600 mutated melanoma.Patients with rare BRAF mutations can respond to targeted therapy, however, efficacy seems to be lower compared with V600E mutated melanoma. Combination BRAFi/MEKi seems to be the best regimen for both V600 and non-V600 mutations. Yet interpretation should be done with care because of the heterogeneity of patients with small sample sizes for some of the reported mutations.

Note: 37(33):3142-3151

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Contributing Institute(s):

1. Biostatistik (C060)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2019

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 25 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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