Analyses of Radiographic Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer
As reported in JAMA Oncology by Rathkopf et al, sensitivity analyses of radiographic progression-free survival in the PREVAIL trial comparing enzalutamide vs placebo in metastatic castration-resistant prostate cancer support use of the measure as a clinically meaningful endpoint in trials in this setting.
Study Details
The PREVAIL trial showed that enzalutamide was associated with significant improvements in overall survival (hazard ratio [HR] = 0.71, P < .001) and radiographic progression-free survival, as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2; HR = 0.19, P < .001). In the trial, 1,717 patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of cytotoxic chemotherapy or an investigational agent. The current study includes prespecified sensitivity analyses to evaluate the clinical utility of the radiographic progression-free survival endpoint.
Sensitivity Analyses
Sensitivity analyses of investigator-assessed radiographic progression-free survival at final data cutoff (439 events) and at the interim overall survival data cutoff (540 events) yielded hazard ratios (HRs) for radiographic progression or death for enzalutamide vs placebo of 0.22 (P < .001) and 0.31 (P < .001). Additional sensitivity analyses using investigator-assessed radiographic progression-free survival as of the final data cutoff found HRs of 0.21, 0.21, 0.23, and 0.23 (all P < .001) when skeletal-related events or any use of radiation or antineoplastic therapy, clinical progression, a confirmatory scan for soft-tissue disease progression, and all deaths regardless of time after study drug discontinuation were included as radiographic progression-free survival events.
Spearman ρ and Kendall τ correlations of radiographic progression-free survival and overall survival in the enzalutamide group were 0.89 and 0.72. Agreement at the final radiographic progression-free survival data cutoff between independent and investigator assessments for progressive and nonprogressive disease was 87.6% overall, including 90.9% in the enzalutamide group and 84.0% in the placebo group.
The investigators concluded, “Sensitivity analyses in PREVAIL demonstrated the robustness of the PCWG2 [radiographic progression-free survival] definition using additional measures of progression. There was concordance between central and investigator review and a positive correlation between [radiographic progression-free survival] and [overall survival] among enzalutamide-treated patients.”
The PREVAIL trial and analyses presented in the JAMA Oncology article were supported by Pfizer Inc and Astellas Pharma, Inc.
Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
