PURPOSE On August 2, 2017, the Food and Drug Administration approved ibrutinib (IMBRUVICA) for the treatment of patients with chronic graft versus host disease (cGVHD) after the failure of one or more lines of systemic therapy. The approval was based on results from a single-arm, multicenter trial that enrolled patients with refractory cGVHD. This paper describes the FDA review of patient-reported outcomes (PRO) data from Study PCYC-1129-CA and the decision to incorporate descriptive PRO data in the FDA label to support the primary clinician-reported outcome results. METHODS In this trial, the Lee Chronic GVHD Symptom Scale (LSS) was used to capture patient-reported symptom bother. The 42 patients who received treatment were included in the analysis and completed the PRO tool. Post hoc descriptive analyses were conducted to further understand the measurement properties of the LSS. RESULTS The analysis submitted to FDA reported that 18 patients had a ≥ 7-point improvement on the LSS overall summary score at any point during the assessment period. For 10 patients, the ≥ 7-point improvement was sustained for ≥ 2 consecutive PRO assessments. An assessment of the responder threshold suggested the threshold submitted to the FDA was reasonable and in line with clinical findings. CONCLUSIONS Overall, study PCYC-1129-CA demonstrated favorable clinician-reported cGVHD efficacy results that were complemented by results from PRO data, supporting the FDA's positive benefit-risk assessment leading to regular approval. Limitations included the single-arm trial design, responder definition, and instrument shortcomings. These limitations were thoroughly explored through additional FDA post hoc analyses.

中文翻译：

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FDA对依鲁替尼治疗慢性移植物抗宿主病的患者报告的结果进行了总结。

目的2017年8月2日，美国食品药品管理局批准了依鲁替尼（IMBRUVICA）用于治疗一种或多种系统治疗失败后的慢性移植物抗宿主病（cGVHD）患者。批准是基于一项单臂，多中心试验的结果，该试验招募了难治性cGVHD患者。本文介绍了FDA对研究PCYC-1129-CA的患者报告结果（PRO）数据的审查，以及将描述性PRO数据纳入FDA标签以支持主要临床医生报告结果的决定。方法在该试验中，使用Lee慢性GVHD症状量表（LSS）来捕获患者报告的症状困扰。分析中包括接受治疗的42位患者，并完成了PRO工具。进行了事后描述性分析，以进一步了解LSS的测量特性。结果提交给FDA的分析报告称，在评估期间的任何时间点，有18例患者的LSS总体总结得分提高了≥7分。对于10位患者，连续≥2次PRO评估持续≥7分。对反应者阈值的评估表明，提交给FDA的阈值是合理的，并且与临床结果一致。结论总体而言，研究PCYC-1129-CA证明了临床医生报告的良好cGVHD疗效结果，并得到了PRO数据的补充，支持FDA的正受益风险评估，从而导致了常规批准。局限性包括单臂试验设计，响应者定义和仪器缺点。