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Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results

Journal Article


Abstract


  • 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.

UOW Authors


  •   De Souza, Paul (external author)

Publication Date


  • 2015

Citation


  • Morris, M. J., Molina, A., Small, E. J., De Bono, J. S., Logothetis, C. J., Fizazi, K., . . . Ryan, C. J. (2015). Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results. Journal of Clinical Oncology, 33(12), 1356-1363. doi:10.1200/JCO.2014.55.3875

Scopus Eid


  • 2-s2.0-84925322822

Web Of Science Accession Number


Start Page


  • 1356

End Page


  • 1363

Volume


  • 33

Issue


  • 12

Place Of Publication


Abstract


  • 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.

UOW Authors


  •   De Souza, Paul (external author)

Publication Date


  • 2015

Citation


  • Morris, M. J., Molina, A., Small, E. J., De Bono, J. S., Logothetis, C. J., Fizazi, K., . . . Ryan, C. J. (2015). Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results. Journal of Clinical Oncology, 33(12), 1356-1363. doi:10.1200/JCO.2014.55.3875

Scopus Eid


  • 2-s2.0-84925322822

Web Of Science Accession Number


Start Page


  • 1356

End Page


  • 1363

Volume


  • 33

Issue


  • 12

Place Of Publication