Cella D, Ivanescu C, Holmstrom S, Bui C N, Spalding J, Fizazi K
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA.
Consulting, Quintiles, Hoofddorp.
Ann Oncol. 2015 Jan;26(1):179-185. doi: 10.1093/annonc/mdu510. Epub 2014 Oct 30.
To present longitudinal changes in Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores during 25-week treatment with enzalutamide or placebo in men with progressive metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy in the AFFIRM trial.
Patients were randomly assigned to enzalutamide 160 mg/day or placebo. FACT-P was completed before randomization, at weeks 13, 17, 21, and 25, and every 12 weeks thereafter while on study treatment. Longitudinal changes in FACT-P scores from baseline to 25 weeks were analyzed using a mixed effects model for repeated measures (MMRM), with a pattern mixture model (PMM) applied as secondary analysis to address non-ignorable missing data. Cumulative distribution function (CDF) plots were generated and different methodological approaches and models for handling missing data were applied. Due to the exploratory nature of the analyses, adjustments for multiple comparisons were not made. AFFIRM is registered with ClinicalTrials.gov, number NCT00974311.
The intention-to-treat FACT-P population included 938 patients (enzalutamide, n = 674; placebo n = 264) with evaluable FACT-P assessments at baseline and ≥1 post-baseline assessment. After 25 weeks, the mean FACT-P total score decreased by 1.52 points with enzalutamide compared with 13.73 points with placebo (P < 0.001). In addition, significant treatment differences at week 25 favoring enzalutamide were evident for all FACT-P subscales and indices, whether analyzed by MMRM or PMM. CDF plots revealed differences favoring enzalutamide compared with placebo across the full range of possible response levels for FACT-P total and all disease- and symptom-specific subscales/indices.
In men with progressive mCRPC after docetaxel-based chemotherapy, enzalutamide is superior to placebo in health-related quality-of-life outcomes, regardless of analysis model or threshold selected for meaningful response.
NCT00974311.
在AFFIRM试验中，呈现接受恩杂鲁胺或安慰剂治疗25周期间，化疗后病情进展的转移性去势抵抗性前列腺癌（mCRPC）男性患者的癌症治疗功能评估-前列腺（FACT-P）评分的纵向变化。
患者被随机分配至每日服用160mg恩杂鲁胺或安慰剂组。FACT-P在随机分组前、第13、17、21和25周完成，此后在研究治疗期间每12周完成一次。使用重复测量混合效应模型（MMRM）分析从基线到25周FACT-P评分的纵向变化，并应用模式混合模型（PMM）作为次要分析以处理不可忽略的缺失数据。生成累积分布函数（CDF）图，并应用不同的方法学方法和模型处理缺失数据。由于分析具有探索性，未进行多重比较调整。AFFIRM已在ClinicalTrials.gov注册，注册号为NCT00974311。
意向性治疗FACT-P人群包括938例患者（恩杂鲁胺组，n = 674；安慰剂组，n = 264），这些患者在基线时有可评估的FACT-P评估且基线后至少有1次评估。25周后，恩杂鲁胺组FACT-P总分平均下降1.52分，而安慰剂组下降13.73分（P < 0.001）。此外，无论通过MMRM还是PMM分析，在第25周时，所有FACT-P子量表和指数均显示出有利于恩杂鲁胺的显著治疗差异。CDF图显示，在FACT-P总分以及所有疾病和症状特异性子量表/指数的所有可能反应水平范围内，与安慰剂相比，恩杂鲁胺更具优势。
在接受多西他赛化疗后病情进展的mCRPC男性患者中，无论选择何种分析模型或有意义反应的阈值，恩杂鲁胺在健康相关生活质量结局方面均优于安慰剂。
NCT00974311。
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