Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study

D. Schadendorf*, M. M. Amonkar, M. Milhem, K. Grotzinger, L. V. Demidov, P. Rutkowski, C. Garbe, R. Dummer, J. C. Hassel, P. Wolter, P. Mohr, U. Trefzer, C. Lefeuvre-Plesse, A. Rutten, N. Steven, G. Ullenhag, L. Sherman, F. S. Wu, K. Patel, M. CaseyC. Robert

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


Background: In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma.

Patients and methods: Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire.

Results: In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4-5 points with chemotherapy but improved by 2-3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8-11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4-8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11-12 points), insomnia (10-12 points), and appetite loss (1-5 points), whereas those for diarrhea worsened (15-16 points). Mixed-model repeated-measures analyses showed significant (P <0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent.

Conclusions: This first QOL assessment for a MEK inhibitor in metastatic melanoma demonstrated that trametinib was associated with less functional impairment, smaller declines in health status, and less exacerbation of symptoms versus chemotherapy.

Original languageEnglish
Article numbermdt580
Pages (from-to)700-706
Number of pages7
JournalAnnals of Oncology
Issue number3
Early online date6 Feb 2014
Publication statusPublished - Mar 2014


  • BRAF
  • Chemotherapy
  • MEK
  • Melanoma
  • Quality of life
  • Trametinib

ASJC Scopus subject areas

  • Oncology
  • Hematology


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