TY - JOUR
T1 - Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer
T2 - COU-AA-302 results
AU - Morris, Michael J.
AU - Molina, Arturo
AU - Small, Eric J.
AU - De Bono, Johann S.
AU - Logothetis, Christopher J.
AU - Fizazi, Karim
AU - De Souza, Paul
AU - Kantoff, Philip W.
AU - Higano, Celestia S.
AU - Li, Jinhui
AU - Kheoh, Thian
AU - Larson, Steven M.
AU - Matheny, Shannon L.
AU - Naini, Vahid
AU - Burzykowski, Tomasz
AU - Griffin, Thomas W.
AU - Scher, Howard I.
AU - Ryan, Charles J.
N1 - Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
PY - 2015/4/20
Y1 - 2015/4/20
N2 - Purpose: Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC. Patients and Methods: rPFS was defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation. Results: A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P <.001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P <.001 and HR, 0.53; 95% CI, 0.45 to 0.62; P <.001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72. Conclusion: rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials.
AB - Purpose: Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC. Patients and Methods: rPFS was defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation. Results: A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P <.001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P <.001 and HR, 0.53; 95% CI, 0.45 to 0.62; P <.001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72. Conclusion: rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials.
UR - http://www.scopus.com/inward/record.url?scp=84925322822&partnerID=8YFLogxK
U2 - 10.1200/JCO.2014.55.3875
DO - 10.1200/JCO.2014.55.3875
M3 - Article
C2 - 25624432
AN - SCOPUS:84925322822
SN - 0732-183X
VL - 33
SP - 1356
EP - 1363
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 12
ER -