D Schadendorf1, M M Amonkar2, M Milhem3, K Grotzinger2, L V Demidov4, P Rutkowski5, C Garbe6, R Dummer7, J C Hassel8, P Wolter9, P Mohr10, U Trefzer11, C Lefeuvre-Plesse12, A Rutten13, N Steven14, G Ullenhag15, L Sherman2, F S Wu2, K Patel2, M Casey2, C Robert16. 1. Department of Dermatology, University Hospital Essen, Essen, Germany. Electronic address: dirk.schadendorf@uk-essen.de. 2. Global Health Outcomes, Oncology Research and Development, and Clinical Statistics, GlaxoSmithKline, Collegeville. 3. Department of Internal Medicine, University of Iowa Hospital and Clinics, Iowa City, USA. 4. Department of Tumor Biotherapy, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation. 5. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. 6. Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. 7. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 8. Department of Dermatology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. 9. Department of General Medical Oncology and Laboratory of Experimental Oncology, University Hospitals, Leuven Cancer Institute, Leuven, Belgium. 10. Department of Dermato-Oncology, Elbekliniken, Buxtehude. 11. Department of Dermatology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 12. Department of Medical Oncology, Centre Eugène Marquis, Rennes, France. 13. Department of Oncology, Sint-Augustinus, Wilrijk, Belgium. 14. The Wellcome Trust Clinical Research Facility, The Queen Elizabeth Hospital, Birmingham, UK. 15. Department of Oncology, Uppsala University, Uppsala, Sweden. 16. Department of Dermatology and U 981, Institut Gustave Roussy, Villejuif-Paris-Sud, France.
Abstract
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.
RCT Entities:
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 (BRAFV600E+, 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.
Entities:
Keywords:
BRAF; MEK; chemotherapy; melanoma; quality of life; trametinib
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