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Radiographic Progression-Free Survival as a Clinically
Meaningful End Point in Metastatic Castration-Resistant
Prostate Cancer
The PREVAIL Randomized Clinical Trial
Dana E. Rathkopf, MD; Tomasz M. Beer, MD; Yohann Loriot, MD, PhD; Celestia S. Higano, MD; Andrew J. Armstrong, MD, ScM; Cora N. Sternberg, MD;
Johann S. de Bono, MB ChB, PhD; Bertrand Tombal, MD, PhD; Teresa Parli, MD; Suman Bhattacharya, PhD; De Phung, BSc; Andrew Krivoshik, MD, PhD;
Howard I. Scher, MD; Michael J. Morris, MD
IMPORTANCE
Drug development for metastatic castration-resistant prostate cancer has been
limited by a lack of clinically relevant trial end points short of overall survival (OS).
Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials
Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful
benefit to patients.
OBJECTIVE
To demonstrate the robustness of the PCWG2 definition and to examine the
relationship between rPFS and OS.
DESIGN, SETTING, AND PARTICIPANTS
PREVAIL was a phase 3, randomized, double-blind,
placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with
metastatic castration-resistant prostate cancer from September 2010 through September
2012. The data were analyzed in November 2016.
INTERVENTIONS
Patients were randomized 1:1 to enzalutamide 160 mg or placebo until
Supplemental content
Research
JAMA Oncology |
Original Investigation
own right is essential to ensure the timely development of COU-AA-302 trial alsodemonstrateda correlati
Table 2. Correlation of Radiogr phic Progr ssion-Free Survival With Overall Survival
a
Method
Correlation (95% CI)
Total
(N = 1717)
Enzalutamide
(n = 872)
Placebo
(n = 845)
Spearman ρ
0.72 (0.67-0.76)
0.89 (0.86-0.92)
0.53 (0.43-0.61)
Kendall τ
0.53 (0.49-0.57)
0.72 (0.68-0.77)
0.37 (0.30-0.44)
a
The analysis da
September 16,
100
80
60
40
20
0
rPFS, %
0
3
6
9
12
21
18
Time, mo
15
No. at risk
Enzalutamide
Placebo
832
801
513
335
259
109
128
33
34
9
4
0
1
0
0
0
100
80
60
40
20
0
rPFS, %
0
3
6
9
12
Time, mo
No. at risk
Enzalutamide
Placebo
832
801
515
339
262
116
131
37
37
10
All intention-to-treat population; data cutoff, May 6, 2012.
rPFS MAY PREDICT OS
Rathkopf DE, et al. JAMA Oncol 2018;4(5):694-701