TY - JOUR
T1 - Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer
T2 - Post hoc analysis of COU-AA-301 and COU-AA-302
AU - Cella, D.
AU - Traina, S.
AU - Li, T.
AU - Johnson, K.
AU - Ho, K. F.
AU - Molina, A.
AU - Shore, N. D.
N1 - Funding Information:
Writing assistance was provided by Lashon Pringle, PhD, and Ann Tighe, PhD, of PAREXEL and was funded by Janssen Global Services, LLC.
Funding Information:
DC is a consultant to Abbvie, Astellas, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Inc, Evidera, GlaxoSmithKline, Helsinn, Ipsen, Janssen Research & Development and Novartis, and is the president of FACIT.org. ST and TL are employees of Janssen Global Services and hold stock in Johnson & Johnson. KJ and AM were employees of Janssen Global Services and held stock in Johnson & Johnson at the time of the analysis. KFH has served as a consultant to Janssen Global Services. NDS has received research funding from and has served as a consultant to Astellas Pharma, Bayer, Dendreon, Ferring Pharmaceuticals, Janssen Research & Development, Medivation and Sanofi.
Funding Information:
Janssen Research & Development (no grant number applies). The sponsor played a role in the design and conduct of the study; in the collection, management, analysis, and interpretation of data; and in the preparation, review, and approval of the manuscript.
Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Metastatic castration-resistant prostate cancer
KW - Overall survival
KW - Pain
KW - Patient-reported outcomes
KW - Quality of life
KW - Radiographic progression-free survival
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U2 - 10.1093/annonc/mdx759
DO - 10.1093/annonc/mdx759
M3 - Article
C2 - 29237083
AN - SCOPUS:85042560713
VL - 29
SP - 392
EP - 397
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 2
ER -