Schadendorf D, Amonkar M M, Milhem M, Grotzinger K, Demidov L V, Rutkowski P, Garbe C, Dummer R, Hassel J C, Wolter P, Mohr P, Trefzer U, Lefeuvre-Plesse C, Rutten A, Steven N, Ullenhag G, Sherman L, Wu F S, Patel K, Casey M, Robert C
Department of Dermatology, University Hospital Essen, Essen, Germany.
Global Health Outcomes, Oncology Research and Development, and Clinical Statistics, GlaxoSmithKline, Collegeville.
Ann Oncol. 2014 Mar;25(3):700-706. doi: 10.1093/annonc/mdt580. Epub 2014 Feb 6.
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' 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.
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.
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.
在一项随机III期研究中，与化疗相比，曲美替尼可延长BRAF V600突变阳性黑色素瘤患者的无进展生存期并改善总生存期。
使用欧洲癌症研究与治疗组织核心生活质量问卷在基线和随访时评估患者的生活质量（QOL）。
在主要疗效人群（BRAF V600E+，无脑转移）中，从基线到第6周和第12周，化疗组患者的总体健康状况评分恶化了4 - 5分，而曲美替尼组患者的评分改善了2 - 3分。化疗组患者的生活质量功能（如角色功能，在第6周和第12周下降8 - 11分）迅速且显著降低，症状加重（如疲劳，第6周和第12周均为4 - 8分；恶心和呕吐，第6周和第12周均为5分）。相比之下，曲美替尼组患者在第12周时，根据功能维度和症状，报告与基线相比有小的改善或轻微恶化。化疗组患者的平均症状量表评分在第6周时，八项症状中有七项（除失眠外）较基线升高（症状恶化），在第12周时，八项症状中有六项（除呼吸困难和失眠外）较基线升高。相比之下，在第6周和第12周时，曲美替尼组患者的疼痛（11 - 12分）、失眠（10 - 12分）和食欲减退（1 - 5分）的平均症状量表评分较基线下降（症状改善），而腹泻的评分恶化（15 - 16分）。混合模型重复测量分析显示，在第6周和/或第12周时，与基线相比，曲美替尼在总体健康、身体、角色和社会功能、疲劳、疼痛、失眠、恶心和呕吐、便秘、呼吸困难及食欲方面有显著（P < 0.05）和/或具有临床意义的改善（小至中度）。意向性治疗人群的生活质量结果一致。
这是首次对转移性黑色素瘤中一种MEK抑制剂进行的生活质量评估，结果表明与化疗相比，曲美替尼导致的功能损害更少，健康状况下降幅度更小，症状加重程度更低。
