Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial
Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial
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DOI：
10.1016/s1470-2045(15)00087-x
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发表时间：
2015-10-01
期刊：
影响因子：
51.1
通讯作者：
Robert, Caroline
中科院分区：
文献类型：
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作者：
Grob, Jean Jacques;Amonkar, Mayur M.;Robert, Caroline
背景在COMBI-v试验中，既往未接受过治疗的BRAF Val 600 Glu或Val 600 Lys突变型不可切除或转移性黑色素瘤患者接受达拉非尼和曲美替尼联合治疗的总生存期和无进展生存期显著长于单用维罗非尼治疗的患者。在这里，我们提出了治疗对健康相关的生活质量（HRQoL）的影响，这是COMBI-v研究中的一个探索性终点。方法COMBI-v是一项开放标签、随机化的3期研究，其中704例BRAF Val 600突变的转移性黑色素瘤患者被随机分配（1：1）通过交互式语音应答系统接收达拉非尼的组合（150 mg每日两次）和曲美替尼（2 mg每日一次）或维罗非尼单药治疗（960 mg每日两次）口服作为一线治疗。主要终点是总生存期。在这项预先规定的探索性分析中，我们使用欧洲癌症研究与治疗组织生活质量量表（EORTC QLQ-C30）、EuroQoL-5D（EQ-5D）和癌症治疗功能评估-黑色素瘤（FACT-M）的黑色素瘤子量表，在基线、研究治疗期间、疾病进展时和进展后完成了对意向治疗人群的HRQoL的前瞻性评估。我们使用混合模型，重复测量ANCOVA来评估组间平均评分的差异，基线评分作为协变量;所有p值均为描述性的。COMBI-V试验注册于ClinicalTrials.gov，注册号NCT 01597908，目前正在进行主要终点试验，但未招募患者。结果从2012年6月4日至2013年10月7日，对全球193个中心的1645名患者进行了合格性筛选，其中704名患者随机分配至达拉非尼加曲美替尼组（n=352）或维罗非尼组（n=352）。两组的问卷完成率均较高（基线时>95%，随访评估时>80%，疾病进展时>70%），两个治疗组在基线时报告的所有问卷的HRQoL和症状评分相似。在研究治疗期间和疾病进展时，在所有三个问卷的大多数领域，治疗组之间的平均评分差异显著且具有临床意义，有利于联合治疗与维罗非尼单药治疗相比，包括EORTC QLQ-C30总体健康（第8周、第16周、第18周和第19周分别为7.92、7.62、6.86、7.47、5.16、7.56和7.57）。24、32、40、48和疾病进展; p
Background In the COMBI-v trial, patients with previously untreated BRAF Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were treated with the combination of dabrafenib and trametinib had significantly longer overall and progression-free survival than those treated with vemurafenib alone. Here, we present the effects of treatments on health-related quality of life (HRQoL), an exploratory endpoint in the COMBI-v study.Methods COMBI-v was an open-label, randomised phase 3 study in which 704 patients with metastatic melanoma with a BRAF Val600 mutation were randomly assigned (1: 1) by an interactive voice response system to receive either a combination of dabrafenib (150 mg twice-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy (960 mg twice-daily) orally as first-line therapy. The primary endpoint was overall survival. In this pre-specified exploratory analysis, we prospectively assessed HRQoL in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer quality of life (EORTC QLQ-C30), EuroQoL-5D (EQ-5D), and Melanoma Subscale of the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), completed at baseline, during study treatment, at disease progression, and after progression. We used a mixed-model, repeated measures ANCOVA to assess differences in mean scores between groups with baseline score as covariate; all p-values are descriptive. The COMBI-v trial is registered with ClinicalTrials.gov, number NCT01597908, and is ongoing for the primary endpoint, but is not recruiting patients.Findings From June 4, 2012, to Oct 7, 2013, 1645 patients at 193 centres worldwide were screened for eligibility, and 704 patients were randomly assigned to dabrafenib plus trametinib (n=352) or vemurafenib (n=352). Questionnaire completion rates for both groups were high (>95% at baseline, >80% at follow-up assessments, and >70% at disease progression) with similar HRQoL and symptom scores reported at baseline in both treatment groups for all questionnaires. Differences in mean scores between treatment groups were signifi cant and clinically meaningful in favour of the combination compared with vemurafenib monotherapy for most domains across all three questionnaires during study treatment and at disease progression, including EORTC QLQ-C30 global health (7.92, 7.62, 6.86, 7.47, 5.16, 7.56, and 7.57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p