A post hoc analysis of radiographic progression with nonrising prostate-specific antigen in patients with metastatic castration-resistant prostate cancer (mCRPC) in the PREVAIL study

Background

Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple pathways. Prostate-specific antigen (PSA) level is the most widely used parameter for disease monitoring, but it has well-recognized limitations including discordant results when compared with imaging studies. We performed the first systematic quantification of patients (pts) with nonrising PSA (nrPSA) at radiographic progression (RP) while on enzalutamide in the multinational, randomized controlled PREVAIL study.

Methods

Chemotherapy-naïve men (n = 872) with mCRPC treated with enzalutamide were analyzed post hoc to identify those with rising PSA (rPSA) versus nrPSA (ie, >1.05 vs ≤1.05 times the PSA level from 3 months earlier) at the time of RP. Pts received oral enzalutamide 160 mg/day plus androgen deprivation therapy. Clinical characteristics and disease outcomes, including the main outcome measures of progression-free survival (PFS) and overall survival (OS), were compared between the rPSA and nrPSA groups.

Results

Of 265 PREVAIL pts with RP and evaluable PSA levels in the enzalutamide arm, 19% had an nrPSA. Baseline clinical characteristics of the 2 groups were similar. Median PFS in the nrPSA group was 8.3 months vs 11.1 months in the rPSA group (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.26-2.23). Overall survival was similar between the 2 groups (not yet reached vs 32.4 months; HR, 0.68; 95% CI, 0.37-1.26). Notably, in pts who had bone-only disease at study entry, 40.3% (31/77) developed soft-tissue disease at progression.

Conclusions

Nonrising PSA at RP is a common phenomenon in pts with mCRPC treated with enzalutamide, but its influence on OS is indeterminate. The high rate of development of new soft tissue disease in pts without prior measurable disease is also notable. It is important to use surveillance imaging rather than relying on PSA alone to monitor pts with mCRPC. Whether nrPSA progression represents a genotypically distinct process with implications for clinical decision-making remains speculative.

Clinical trial identification

NCT01212991

Legal entity responsible for the study

Medivation, Inc. and Astellas Pharma, Inc.

Funding

Medivation, Inc. and Astellas Pharma, Inc.

Disclosure

A. Armstrong: reports grants and personal fees from Medivation/Astellas, Janssen, Dendreon, Sanofi Aventis, Bayer.

C.S. Higano: reports consultant or advisory role with Astellas, Medivation; research funding from Medivation; other from Astellas, Medivation.

P. Iversen: reports funding from Astellas, Medivation during the conduct of the study; personal fees from janssen, Ferring outside the submitted work.

C.N. Sternberg: reports personal fees from Astellas, during the conduct of the study; personal fees from Johnson & Johnson, personal fees from Ipsen, personal fees from Bayer, personal fees from Millenium, outside the submitted work.

D.E. Rathkopf: reports grants from Medivation, during the conduct of the study; grants from Janssen, Medivation, Millenium, Celgene, Novartis, Ferring, outside the submitted work.

Y. Loriot: reports personal fees from Medivation, Astellas, Sanofi, Janssen, Oncogenex, Bayer, Ipsen, outside the submitted work.

J. de Bono: reports personal fees from Astellas.

B. Tombal: reports grants, personal fees and non-financial support from Astellas, personal fees from Medivation personal fees from Bayer, grants and personal fees from Ferring, grants and personal fees from Sanofi, outside the submitted work.

S. Abhyankar: reports personal fees from Medivation, during the conduct of the study; personal fees from Medivation, Inc, outside the submitted work.

P. Lin: is a Medivation employee.

A. Krivoshik: employee of Astellas and hold stock in Abbott and Abbvie.

D. Phung: is an Astellas employee.

T.M. Beer: reports grants from Astellas, Medivation, Janssen, during the conduct of the study; personal fees from Janssen Japan, Astellas, other from Medivation, Astellas to participate in a certified nursing education program, outside the submitted work.

All other authors have declared no conflicts of interest.