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000147211 0247_ $$2doi$$a10.1200/JCO.19.00489
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000147211 0247_ $$2ISSN$$a0732-183X
000147211 0247_ $$2ISSN$$a1527-7755
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000147211 037__ $$aDKFZ-2019-02337
000147211 041__ $$aeng
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000147211 1001_ $$aMenzer, Christian$$b0
000147211 245__ $$aTargeted Therapy in Advanced Melanoma With Rare BRAF Mutations.
000147211 260__ $$aAlexandria, Va.$$bAmerican Society of Clinical Oncology$$c2019
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000147211 500__ $$a37(33):3142-3151
000147211 520__ $$aBRAF/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.
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000147211 7001_ $$aMenzies, Alexander M$$b1
000147211 7001_ $$aCarlino, Matteo S$$b2
000147211 7001_ $$aReijers, Irene$$b3
000147211 7001_ $$aGroen, Emma J$$b4
000147211 7001_ $$aEigentler, Thomas$$b5
000147211 7001_ $$ade Groot, Jan Willem B$$b6
000147211 7001_ $$avan der Veldt, Astrid A M$$b7
000147211 7001_ $$aJohnson, Douglas B$$b8
000147211 7001_ $$aMeiss, Frank$$b9
000147211 7001_ $$aSchlaak, Max$$b10
000147211 7001_ $$aSchilling, Bastian$$b11
000147211 7001_ $$aWestgeest, Hans M$$b12
000147211 7001_ $$aGutzmer, Ralf$$b13
000147211 7001_ $$aPföhler, Claudia$$b14
000147211 7001_ $$aMeier, Friedegund$$b15
000147211 7001_ $$aZimmer, Lisa$$b16
000147211 7001_ $$aSuijkerbuijk, Karijn P M$$b17
000147211 7001_ $$aHaalck, Thomas$$b18
000147211 7001_ $$aThoms, Kai-Martin$$b19
000147211 7001_ $$aHerbschleb, Karin$$b20
000147211 7001_ $$aLeichsenring, Jonas$$b21
000147211 7001_ $$aMenzer, Alexander$$b22
000147211 7001_ $$0P:(DE-He78)bb6a7a70f976eb8df1769944bf913596$$aKopp-Schneider, Annette$$b23$$udkfz
000147211 7001_ $$aLong, Georgina V$$b24
000147211 7001_ $$aKefford, Richard$$b25
000147211 7001_ $$aEnk, Alexander$$b26
000147211 7001_ $$aBlank, Christian U$$b27
000147211 7001_ $$aHassel, Jessica C$$b28
000147211 773__ $$0PERI:(DE-600)2005181-5$$a10.1200/JCO.19.00489$$gp. JCO.19.00489 -$$n33$$p3142-3151$$tJournal of clinical oncology$$v37$$x1527-7755$$y2019
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