Bellinda L King-Kallimanis1,2, Tanya Wroblewski3, Virginia Kwitkowski3, R Angelo De Claro3, Thomas Gwise3, Vishal Bhatnagar3, Ann T Farrell3, Paul G Kluetz4. 1. Oncology Center of Excellence, U.S. Food and Drug Administration, Building 22, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA. belinda.kallimanis@fda.hhs.gov. 2. U.S. Food and Drug Administration, WO22 Room 2372, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA. belinda.kallimanis@fda.hhs.gov. 3. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, USA. 4. Oncology Center of Excellence, U.S. Food and Drug Administration, Building 22, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Abstract
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.
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.
Authors: Nathaniel Edward Bennett Saidu; Chiara Bonini; Anne Dickinson; Magdalena Grce; Marit Inngjerdingen; Ulrike Koehl; Antoine Toubert; Robert Zeiser; Sara Galimberti Journal: Front Immunol Date: 2020-10-09 Impact factor: 7.561