Title | The Effect of Corticosteroids on Prostate Cancer Outcome Following Treatment with Enzalutamide: A Multivariate Analysis of the Phase III AFFIRM Trial. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Zhao JL, Fizazi K, Saad F, Chi KN, Taplin M-E, Sternberg CN, Armstrong AJ, de Bono JS, Duggan WT, Scher HI |
Journal | Clin Cancer Res |
Volume | 28 |
Issue | 5 |
Pagination | 860-869 |
Date Published | 2022 Mar 01 |
ISSN | 1557-3265 |
Keywords | Adrenal Cortex Hormones, Antineoplastic Agents, Benzamides, Disease-Free Survival, Humans, Male, Multivariate Analysis, Nitriles, Phenylthiohydantoin, Prostatic Neoplasms, Castration-Resistant, Treatment Outcome |
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. |
DOI | 10.1158/1078-0432.CCR-21-1090 |
Alternate Journal | Clin Cancer Res |
PubMed ID | 34965947 |
PubMed Central ID | PMC9366341 |
Grant List | P50 CA092629 / CA / NCI NIH HHS / United States 20YOUN22 / / Prostate Cancer Foundation Young Investigator Award / P30 CA008748 / CA / NCI NIH HHS / United States P50-CA92629 / GF / NIH HHS / United States K12CA184746 / / Paul Calabresi Career Development Award for Clinical Oncology / |