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


ŞENGÜL SAMANCI N. , ÇELİK E. , BAĞCILAR Ö. , EROL B. Ç. , Bicki E., ORUÇ K. , ...More

Melanoma research, vol.30, no.5, pp.477-483, 2020 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 30 Issue: 5
  • Publication Date: 2020
  • Doi Number: 10.1097/cmr.0000000000000678
  • Title of Journal : Melanoma research
  • Page Numbers: pp.477-483

Abstract

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.