Background Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aim to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). Patients and methods We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088). Eligible COU-AA-301 patients had progressed after docetaxel and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Eligible COU-AA-302 patients had no prior chemotherapy and ECOG PS 0 or 1. Patients were treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day) or prednisone alone daily. Association between self-reported fatigue, pain and functional status, and OS and/or rPFS, using pooled data regardless of treatment, was assessed. Cox proportional hazard regression modeled time to death or radiographic progression. Results In COU-AA-301 patients, PRO improvements were associated with longer OS and longer time to radiographic progression versus worsening or stable PROs (P < 0.0001). In multivariate models, all except pain intensity remained associated with OS. Pain intensity, PWB and FWB improvements remained associated with rPFS. In COU-AA-302 patients, worsening PROs were associated with higher likelihood of radiographic progression (P ≤ 0.025) compared with improved or stable PROs. In multivariate models, worsening PWB remained associated with worse rPFS. The 12-month analysis confirmed the 6-month results. Conclusions PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional clinical practice methods for monitoring patients for disease progression.

中文翻译：

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转移性去势抵抗性前列腺癌患者报告的结局与临床结局之间的关系：COU-AA-301和COU-AA-302的事后分析。

背景患者报告的结局（PRO）用于评估药物开发中的获益风险。PRO与临床结果之间的关系尚不清楚。我们旨在阐明转移性去势抵抗性前列腺癌（mCRPC）中PRO措施的变化与临床结局之间的关系。患者和方法我们调查了自我报告的疲劳，疼痛，功能性健康（FWB），身体健康（PWB）和前列腺癌特有症状与总生存期（OS）和无影像学无进展生存期之间的关系（ rPFS）在COU-AA-301（N = 1195）或COU-AA-302（N = 1088）中治疗6和12个月后。符合条件的COU-AA-301患者在多西他赛治疗后进展，并且东部合作肿瘤小组的工作状态（ECOG PS）≤2。符合条件的COU-AA-302患者未曾接受过化学疗法且ECOG PS 0或1。患者接受醋酸阿比特龙（1000 mg /天）加泼尼松（10 mg /天）或泼尼松单独治疗。使用汇总的数据评估自我报告的疲劳，疼痛和功能状态与OS和/或rPFS之间的关联，而与治疗无关。考克斯比例风险回归模型模拟了死亡时间或影像学进展。结果在COU-AA-301患者中，PRO的改善与OS延长和影像学进展时间更长相关，而PRO则恶化或稳定（P <0.0001）。在多变量模型中，除疼痛强度外，所有其他因素均与OS相关。疼痛强度，PWB和FWB改善仍与rPFS相关。在COU-AA-302患者中，与改善或稳定的PRO相比，PRO恶化与放射学进展的可能性更高（P≤0.025）。在多变量模型中，PWB恶化仍与rPFS恶化有关。12个月的分析证实了6个月的结果。结论PROs与临床试验中临床相关的事件发生时间疗效显着相关，并且可以补充和帮助预测用于监测患者疾病进展的传统临床实践方法。