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| 001 | 147211 | ||
| 005 | 20240229112642.0 | ||
| 024 | 7 | _ | |a 10.1200/JCO.19.00489 |2 doi |
| 024 | 7 | _ | |a pmid:31580757 |2 pmid |
| 024 | 7 | _ | |a 0732-183X |2 ISSN |
| 024 | 7 | _ | |a 1527-7755 |2 ISSN |
| 024 | 7 | _ | |a altmetric:67647346 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2019-02337 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Menzer, Christian |b 0 |
| 245 | _ | _ | |a Targeted Therapy in Advanced Melanoma With Rare BRAF Mutations. |
| 260 | _ | _ | |a Alexandria, Va. |c 2019 |b American Society of Clinical Oncology |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1574062550_16953 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a 37(33):3142-3151 |
| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Menzies, Alexander M |b 1 |
| 700 | 1 | _ | |a Carlino, Matteo S |b 2 |
| 700 | 1 | _ | |a Reijers, Irene |b 3 |
| 700 | 1 | _ | |a Groen, Emma J |b 4 |
| 700 | 1 | _ | |a Eigentler, Thomas |b 5 |
| 700 | 1 | _ | |a de Groot, Jan Willem B |b 6 |
| 700 | 1 | _ | |a van der Veldt, Astrid A M |b 7 |
| 700 | 1 | _ | |a Johnson, Douglas B |b 8 |
| 700 | 1 | _ | |a Meiss, Frank |b 9 |
| 700 | 1 | _ | |a Schlaak, Max |b 10 |
| 700 | 1 | _ | |a Schilling, Bastian |b 11 |
| 700 | 1 | _ | |a Westgeest, Hans M |b 12 |
| 700 | 1 | _ | |a Gutzmer, Ralf |b 13 |
| 700 | 1 | _ | |a Pföhler, Claudia |b 14 |
| 700 | 1 | _ | |a Meier, Friedegund |b 15 |
| 700 | 1 | _ | |a Zimmer, Lisa |b 16 |
| 700 | 1 | _ | |a Suijkerbuijk, Karijn P M |b 17 |
| 700 | 1 | _ | |a Haalck, Thomas |b 18 |
| 700 | 1 | _ | |a Thoms, Kai-Martin |b 19 |
| 700 | 1 | _ | |a Herbschleb, Karin |b 20 |
| 700 | 1 | _ | |a Leichsenring, Jonas |b 21 |
| 700 | 1 | _ | |a Menzer, Alexander |b 22 |
| 700 | 1 | _ | |a Kopp-Schneider, Annette |0 P:(DE-He78)bb6a7a70f976eb8df1769944bf913596 |b 23 |u dkfz |
| 700 | 1 | _ | |a Long, Georgina V |b 24 |
| 700 | 1 | _ | |a Kefford, Richard |b 25 |
| 700 | 1 | _ | |a Enk, Alexander |b 26 |
| 700 | 1 | _ | |a Blank, Christian U |b 27 |
| 700 | 1 | _ | |a Hassel, Jessica C |b 28 |
| 773 | _ | _ | |a 10.1200/JCO.19.00489 |g p. JCO.19.00489 - |0 PERI:(DE-600)2005181-5 |n 33 |p 3142-3151 |t Journal of clinical oncology |v 37 |y 2019 |x 1527-7755 |
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| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 23 |6 P:(DE-He78)bb6a7a70f976eb8df1769944bf913596 |
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