796PEARLY PSA RESPONSE IS AN INDEPENDENT PROGNOSTIC FACTOR IN PATIENTS WITH MCRPC TREATED WITH NEXT-GENERATION ANDROGEN PATHWAY INHIBITORS

Abstract Aim: To determine the clinical significance of early PSA response during the first 4 weeks of therapy with next-generation androgen pathway inhibitors (enzalutamide, abiraterone acetate [AA], TAK-700) for metastatic castration-resistance prostate cancer (mCRPC). Methods: Data from patients prospectively recruited in clinical trials were studied. PSA values were obtained at baseline and 28 days (+/- 7d) after treatment initiation. PSA response defined as a decline > 50% from baseline was calculated according to PCWG2 (Scher et al, 2008). The effects of patient, tumor, and treatment characteristics on progression-free survival (PFS) and overall survival (OS) were examined using the Cox model. An independent cohort of patients treated with AA was used as validation population. Results: Early PSA response (EPR) was assessed in 118 patients treated with enzalutamide (AFFIRM and PREVAIL studies), AA (COU-AA-301 and 302 studies) and TAK-700 (C21004 and C21005 study). EPR was associated with longer PFS and OS (P < .0001). Median PFS was 5.6 and 13.9 months (hazard ratio [HR]: 2.6, p < 0.001) for patients without and with an EPR, respectively. Median OS was 16 months in patients without EPR and 32 months in patients with an EPR (HR: 2.0, p < 0.01). EPR remained predictive for OS in multivariate analyses that included pre-therapeutic prognostic factors for mCRPC (ECOG score, visceral disease, pain, albumin, PSA, Alkaline phosphatase, LDH, Hemoglobin; Halabi et al, 2014). Prognostic values of EPR for PFS (HR:1.9, p < 0.01) and OS (HR: 2.8, p < 0.01) were confirmed in a second independent cohort of 95 AA-treated patients. Conclusions: Early PSA response 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. Disclosure: C. Massard: Consultant for Astellas Lectures for Sanofi, Astellas, Janssen; L. Albiges Sauvin: Advisory board Sanofi; K. Fizazi: Consultant Lectures for si, Astellas, Janssen, Takeda; Y. Loriot: Grant from Sanofi, Astelllas, Consultant for Astellas, Sanofi, Sellgene Lectures for Sanofi, Astellas, Janssen. All other authors have declared no conflicts of interest.