Oncology Center of Excellence, U.S. Food and Drug Administration, Building 22, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
U.S. Food and Drug Administration, WO22 Room 2372, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Qual Life Res. 2020 Jul;29(7):1903-1911. doi: 10.1007/s11136-020-02448-y. Epub 2020 Feb 25.
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.
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.
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.
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.
2017 年 8 月 2 日，美国食品和药物管理局（FDA）批准依鲁替尼（Imbruvica）用于治疗接受一种或多种系统治疗后失败的慢性移植物抗宿主病（cGVHD）患者。该批准基于一项单臂、多中心试验的结果，该试验招募了难治性 cGVHD 患者。本文描述了 FDA 对研究 PCYC-1129-CA 中患者报告结局（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局结果的决定。
在这项试验中，Lee 慢性移植物抗宿主病症状量表（LSS）用于捕捉患者报告的症状困扰。接受治疗的 42 名患者被纳入分析并完成了 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。
提交给 FDA 的分析报告称，在评估期的任何时间点，18 名患者的 LSS 总体综合评分至少改善了 7 分。对于 10 名患者，≥7 分的改善在≥2 次连续 PRO 评估中持续存在。对应答者阈值的评估表明，提交给 FDA 的阈值是合理的，与临床发现一致。
总体而言，PCYC-1129-CA 研究显示出有利的临床医生报告的 cGVHD 疗效结果，这些结果得到了 PRO 数据的补充，支持了 FDA 进行积极的获益风险评估，从而获得了常规批准。局限性包括单臂试验设计、应答者定义和仪器缺陷。这些局限性通过额外的 FDA 事后分析进行了彻底探讨。
