Targeted therapy in advanced melanoma with rare BRAF mutations

• Verfasst von: Menzer, Christian [VerfasserIn]
• Verfasst von: Menzies, Alexander M. [VerfasserIn]
• Verfasst von: Carlino, Matteo S. [VerfasserIn]
• Verfasst von: Reijers, Irene [VerfasserIn]
• Verfasst von: Groen, Emma J. [VerfasserIn]
• Verfasst von: Eigentler, Thomas [VerfasserIn]
• Verfasst von: de Groot, Jan Willem B. [VerfasserIn]
• Verfasst von: van der Veldt, Astrid A.M. [VerfasserIn]
• Verfasst von: Johnson, Douglas B. [VerfasserIn]
• Verfasst von: Meiss, Frank [VerfasserIn]
• Verfasst von: Schlaak, Max [VerfasserIn]
• Verfasst von: Schilling, Bastian [VerfasserIn]
• Verfasst von: Westgeest, Hans M. [VerfasserIn]
• Verfasst von: Gutzmer, Ralf [VerfasserIn]
• Verfasst von: Pföhler, Claudia [VerfasserIn]
• Verfasst von: Meier, Friedegund [VerfasserIn]
• Verfasst von: Zimmer, Lisa [VerfasserIn]
• Verfasst von: Suijkerbuijk, Karijn P.M. [VerfasserIn]
• Verfasst von: Haalck, Thomas [VerfasserIn]
• Verfasst von: Thoms, Kai-Martin [VerfasserIn]
• Verfasst von: Herbschleb, Karin [VerfasserIn]
• Verfasst von: Leichsenring, Jonas [VerfasserIn]
• Verfasst von: Menzer, Alexander [VerfasserIn]
• Verfasst von: Kopp-Schneider, Annette [VerfasserIn]
• Verfasst von: Long, Georgina V. [VerfasserIn]
• Verfasst von: Kefford, Richard [VerfasserIn]
• Verfasst von: Enk, Alexander [VerfasserIn]
• Verfasst von: Blank, Christian U. [VerfasserIn]
• Verfasst von: Hassel, Jessica C. [VerfasserIn]
• Titel: Targeted therapy in advanced melanoma with rare BRAF mutations
• Verf.angabe: Christian Menzer, Alexander M. Menzies, Matteo S. Carlino, Irene Reijers, Emma J. Groen, Thomas Eigentler, Jan Willem B. de Groot, Astrid A.M. van der Veldt, Douglas B. Johnson, Frank Meiss, Max Schlaak, Bastian Schilling, Hans M. Westgeest, Ralf Gutzmer, Claudia Pföhler, Friedegund Meier, Lisa Zimmer, Karijn P.M. Suijkerbuijk, Thomas Haalck, Kai-Martin Thoms, Karin Herbschleb, Jonas Leichsenring, Alexander Menzer, Annette Kopp-Schneider, Georgina V. Long, Richard Kefford, Alexander Enk, Christian U. Blank and Jessica C. Hassel
• E-Jahr: 2019
• Jahr: October 03, 2019
• Umfang: 10 S.
• Fussnoten: Gesehen am 18.03.2020
• Titel Quelle: Enthalten in: Journal of clinical oncology / Englische Ausgabe
• Ort Quelle: Alexandria, Va. : American Society of Clinical Oncology, 1983
• Jahr Quelle: 2019
• Band/Heft Quelle: 37(2019), 33, Seite 3142-3151
• ISSN Quelle: 0732-183X
• DOI: doi:10.1200/JCO.19.00489
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1692907085

Abstract

PURPOSE: 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.METHODSIn 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.RESULTSFifty-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.CONCLUSIONPatients 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.