The Effect of Corticosteroids on Prostate Cancer Outcome Following Treatment with Enzalutamide: A Multivariate Analysis of the Phase III AFFIRM Trial

Jimmy L Zhao, Karim Fizazi, Fred Saad, Kim N Chi, Mary-Ellen Taplin, Cora N Sternberg, Andrew J Armstrong, Johann S de Bono, William T Duggan, Howard I Scher, Jimmy L Zhao, Karim Fizazi, Fred Saad, Kim N Chi, Mary-Ellen Taplin, Cora N Sternberg, Andrew J Armstrong, Johann S de Bono, William T Duggan, Howard I Scher

Abstract

Purpose: The clinical impact of concurrent corticosteroid use (CCU) on enzalutamide-treated patients with metastatic castration-resistant prostate cancer (mCRPC) is unknown. We investigated the association of CCU with overall survival (OS), radiographic progression-free survival (rPFS), and time to prostate-specific antigen progression (TTPP) in post-chemotherapy, enzalutamide-treated patients with mCRPC.

Patients and methods: Post hoc analysis of AFFIRM (NCT00974311) with patients (n = 1,199) randomized 2:1 to enzalutamide 160 mg/day or placebo. Treatment group, CCU, and known prognostic factors were evaluated for impact on OS, rPFS, and TTPP using a multivariate Cox proportional hazards model. CCU was defined as "baseline" (use started at baseline) or "on-study" (baseline plus use that was started during the trial).

Results: Enzalutamide significantly improved OS, rPFS, and TTPP independent of baseline CCU but was associated with inferior clinical outcomes when compared with no baseline CCU, including a shorter OS [10.8 months vs. not reached (NR); HR for use vs. no use, 2.13; 95% confidence interval (CI), 1.79-2.54], rPFS (5.2 months vs. 8.0 months; HR, 1.49; 95% CI, 1.29-1.72], and TTPP (4.6 months vs. 5.7 months; HR, 1.50; 95% CI, 1.25-1.81). These findings held in a multivariate analysis adjusting for baseline prognostic factors wherein baseline CCU was independently associated with decreased OS (HR, 1.71; 95% CI, 1.43-2.04; P < 0.0001) and rPFS (HR, 1.28; 95% CI, 1.11-1.48; P = 0.0007).

Conclusions: Patients with mCRPC benefited from enzalutamide treatment independent of CCU, but CCU was associated with worse baseline prognostic factors and outcomes.

©2021 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
OS (A), rPFS (B), and PSA PFS (C), with and without baseline corticosteroid use. NR, not reached.
Figure 2.
Figure 2.
Assessment of treatment-by-baseline corticosteroid use interaction analysis (A) and effects of baseline corticosteroid use on OS, rPFS, and TTPP in patients stratified into high-risk or low-risk groups (B).

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