BRAF-V600 mutations have no prognostic impact in stage IV melanoma patients treated with monochemotherapy

PLoS One. 2014 Feb 20;9(2):e89218. doi: 10.1371/journal.pone.0089218. eCollection 2014.

Abstract

Background: The impact of BRAF tumor mutations on the natural course of disease of melanoma patients is controversial.

Patients and methods: We analyzed the mutational status and overall survival of 215 patients receiving treatment with dacarbazine or temozolomide. All patients who started first-line treatment at our institution between 2000 and 2010 were included to prevent selection and bias due to thereafter arising therapeutic options.

Results: No patient received BRAF- or MEK-inhibitors during follow-up. Survival was associated with the pattern of visceral involvement, the presence of brain metastases and the serum lactate dehydrogenase level (all p<0.001). The BRAF-V600 mutational status was not associated with survival and no differences in overall survival were detected according to age, gender or to the cytotoxic agent used for therapy. In Cox regression analysis the presence of brain metastases (hazard ratio 2.3; p<0.001) and an elevated serum LDH (hazard ratio 2.5; p<0.001) were the only factors, which independently predicted survival.

Conclusions: No differences in prognosis were observed according to the BRAF mutational status in patients with distant metastasis treated with monochemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Melanoma / drug therapy
  • Melanoma / genetics*
  • Melanoma / mortality
  • Melanoma / pathology
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / secondary
  • Survival Rate
  • Temozolomide

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Temozolomide

Grants and funding

Parts of this study were funded by Roche Pharma AG, Grenzach-Wyhlen, Germany. The study was designed in cooperation with the funding company. The funders had no role in the data collection, data analysis, data interpretation, or decision to publish. The final manuscript was provided to the funding company for notification but was not changed in any relevant part thereafter.