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Loss of skeletal muscle area and fat-free mass during dabrafenib/trametinib and vemurafenib/cobimetinib treatments in patients with BRAF-mutant metastatic malignant melanoma

Tarih
2020
Yazar
Demirci, Nebi Serkan
Bedir, Sahin
DEĞERLİ, Ezgi
Derin, Sumeyra
DEMİRELLİ, Fuat Hulusi
ŞENGÜL SAMANCI, Nilay
ÇELİK, Emir
Bagcilar, Omer
Erol, Burak Caglar
Bicki, Ela
ORUÇ, Kerem
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Özet
This study aimed to assess whether dabrafenib/trametinib and vemurafenib/cobimetinib treatments are associated with a change in skeletal muscle area (SMA) and total fat-free mass (FFM) assessed by computed tomography (CT), and to compare the efficacy and safety profile of these treatments in patients with metastatic melanoma. Thirty-one patients treated with B-Raf proto-oncogene, serine/threonine kinase/MAPK extracellular receptor kinase inhibitors were included between 2016 and 2019. Eighteen patients received dabrafenib/trametinib and remaining patients received vemurafenib/cobimetinib. CT scans were performed at baseline and at 4-6 months of follow-up to measure cross-sectional areas of SMA. FFM and skeletal muscle index (SMI) values were calculated. Of the patients, including 18 treated with dabrafenib/trametinib (58.1%) and 13 with vemurafenib/cobimetinib (41.9%); 58.1% were male, 41.9% were female and median age was 52 years. A significant decrease in SMA was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 andP = 0.002, respectively). A significant decrease in FFM values was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 andP = 0.002, respectively). Dose-limiting toxicity (DLT) was observed in 35.9% of the patients with sarcopenia. No significant difference was seen between the dabrafenib/trametinib and vemurafenib/cobimetinib groups in median progression-free survival (PFS) (11.9 vs. 7.3 months, respectively,P = 0.28) and in median overall survival (OS) (25.46 vs. 13.7 months, respectively,P = 0.41). Baseline sarcopenia was not significantly associated with PFS or OS (P = 0.172 andP = 0.326, respectively). We found a significant decrease in SMI values determined at 4-6 months compared to the values before treatment both in dabrafenib/trametinib and vemurafenib/cobimetinib groups. DLT was similar with both treatments. Baseline sarcopenia was not significantly associated with PFS or OS.
Bağlantı
http://hdl.handle.net/20.500.12627/3102
https://doi.org/10.1097/cmr.0000000000000678
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