Long-term survival in patients with metastatic castration resistant prostate cancer (mCRPC) treated with enzalutamide in a named patient programs (NPP)

Abstract

Background: The majority of patients ( pts) with metastatic prostate cancer (mPC) becomes resistant to established androgen deprivation therapies (ADT). Men who develop mCRPC have a poor prognosis. Enzalutamide (ENZ) is one of the most exciting new hormonal agents which demonstrated a survival gain in pts with CRPC. Methods: We retrospectively evaluated a consecutive series of pts with mCRPC who have received ENZ, before his approval in Italy, in a NPP conducted in our hospital. We defined two cohorts of pts depending on overall survival (OS) defined as time of date starting ENZ to date of death/last follow up. Group 1 (G1) included pts with OS 3 14 months and group 2 (G2) included pts with OS < 14 months. Baseline pts characteristics, treatment details and outcomes data were compared in the two groups with the aim to evaluate potential factors outcome-related. Results: From June 2010 to April 2013 18 pts were treated with ENZ in a NPP in our institution. All the pts received docetaxel (TXT) as first line therapy. Median OS for ENZ was 14 months (95% CI 6-22). Each group counts 9 pts. Median age at diagnosis of PC was 65 years (yrs) for G1 and 64 yrs for G2. In both groups 7/9 pts (78%) have Gleason score 3 7. Prostatectomy was performed in 4 pts (44%) of G1 and in 1 pt (11%) of G2 (p = 0.29). Metastatic disease at diagnosis was present in 4 pts (44%) of G1 and in 6 pts (67%) of G2. Metastatic free interval (MFI) was 10 yrs for G1 and 7 yrs for G2 (p = 0.79). As first metastatic site (FMS) nodal involvement is more frequent in the G1 (68%), while bone disease was FMS in the 77% of the pts of G2 (p > 0.05). The median duration of ADT was 5.4 yrs for G1 and 1.7 yrs for G2 (p = 0.51). ENZ was second line therapy in all pts of G1 and in only 4 pts in (p = 0.02). Median prostate-specific antigen (PSA) level before starting ENZ was 45 ng/ml for G1 and 97 ng/ml for G2 (p = 0.66); median PSA nadir level during ENZ was 0.43 ng/ml in G1 and 47 ng/ml in G2 (p = 0,39). PSA response rate 350% was detected in 6 pts (67%) of G1 and in 3 pts (33%) of G2 (p = 0.31). Conclusion: Our preliminary results, even if based on a limited number of pts, suggest that mCRPC pts with radical prostatectomy, nodal involvement as first metastatic site, androgen-deprivation long response, ENZ treatment after TXT (II-line) and ENZ-PSA response rate 350% have a good prognosis with a survival time of more than 14 months. These data should be confirmed in a larger patient population.