Early PSA response is an independent prognostic factor in patients with metastatic castration-resistant prostate cancer treated with next-generation androgen pathway inhibitors.

Abstract

BACKGROUND:

The optimal use of new therapies in metastatic castration-resistant prostate cancer (mCRPC) remains to be clarified. Prostate-specific antigen (PSA) response used as a pharmacodynamic end-point may help identify patients with early resistance to new androgen receptor-pathway inhibitors. We aimed to determine the clinical significance of early PSA response (EPR) during therapy with enzalutamide, abiraterone acetate (AA) and orteronel in mCRPC.

METHODS:

Data from patients recruited in clinical trials were studied. PSA values were obtained at baseline and 28 d after treatment initiation. EPR defined as a decline >50% from baseline was calculated according to the Prostate Cancer Working Group 2 criteria. The effects of clinical characteristics on radiographic progression-free survival (rPFS) and overall survival (OS) were examined using the Cox model.

RESULTS:

EPR was assessed in 118 patients treated in clinical trials and was found to be associated with longer rPFS and OS (P < 0.0001 for both). Median rPFS was 13.9 and 5.6 months (hazard ratio [HR]:0.38, P < 0.001) for patients with and without an EPR, respectively. Median OS was 32.2 months in patients with an EPR and 15.9 months in patients without an EPR (HR: 0.4, P < 0.01). EPR remained prognostic for OS in multivariate analyses (HR: 0.5, p=0.009) that included validated pre-therapeutic prognostic factors for mCRPC. Prognostic values of EPR for rPFS and OS were confirmed in an independent cohort of 95 AA-treated non-trial patients.

CONCLUSIONS:

EPR is an independent prognostic factor in patients with mCRPC treated with next-generation androgen pathway inhibitors and may be useful for the therapeutic management of these patients.

• Authors: Alina Fuerea, Giulia Baciarello, Anna Patrikidou, Laurence Albigès, Christophe Massard, Mario Di Palma, Bernard Escudier, Karim Fizazi, Yohann Loriot
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 61 Pg. 44-51 (07 2016) ISSN: 1879-0852 [Electronic] England
• PMID: 27151554 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Androgen Antagonists
• Benzamides
• Biomarkers, Tumor
• Nitriles
• Phenylthiohydantoin
• enzalutamide
• Prostate-Specific Antigen
• Abiraterone Acetate

Topics

• Abiraterone Acetate (analysis)
• Aged
• Androgen Antagonists (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Benzamides
• Biomarkers, Tumor (blood)
• Disease-Free Survival
• Humans
• Male
• Middle Aged
• Multivariate Analysis
• Nitriles
• Phenylthiohydantoin (administration & dosage, analogs & derivatives)
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms, Castration-Resistant (blood, drug therapy)