A multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first-line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): CHEIRON study.

Abstract

148 Background: D and E demonstrated to be efficacious in the treatment of mCRPC pts. Due to different antitumor mechanism of action of these agents, it could be postulated that their combination can improve disease control. CHEIRON study tried to demonstrate the candidate efficacy of chemo-hormonal combination D+E versus D in mCRPC first-line. Methods: Eligibility criteria included untreated mCRPC diagnosis, ECOG PS ≤ 2, adequate renal, hepatic and hematological functions. Pts were randomized to receive D 75 mg/m2 IV d1 q3w plus prednisone 5 mg PO BID for 8 courses alone or plus E 160 mg PO daily for 24 weeks. Stratification criteria were presence of pain and visceral metastases. The primary endpoint of the study was the rate of pts without disease progression (according to PCWG2) at 6 mos after randomization. Results: Between 09/2014 and 10/2017, 246 pts (median age 70 years, range 44-88, pain reported by 54 pts, visceral metastases present in 50 pts) were randomized to DE (120) or D (126). The rate of pts without disease progression at 6 mos was significantly higher in DE arm compared to D arm [87.3% (CI95% 64-80) vs 72.6% (CI95% 80-92); p = 0.006). Similarly, a higher proportion of DE pts achieved a PSA reduction ≥ 50% compared to the baseline values compared to the D pts [92.2%(CI95% 61-77) vs 70.0%(CI95% 86-96); p < 0.0001). No differences were observed in terms of objective response rate. Major haematological toxicities consisted of grade 3-4 anemia (3 pts DE – 1 pt D) and grade 3-4 neutropenia (23 pts DE – 19 pts D); febrile neutropenia was observed in 10 DE pts and in 5 D pts. At a median follow-up of 20 mos, the median progression free survival was 11.3 mos (CI95% 10.0-12.7) and 9.1 mos (CI95% 8.9-9.2) in DE and D arm, respectively (p = 0.004). In D arm the median overall survival was 30.5 mos (CI95% 24.1-36.8) compared to 28.7 mos (CI95% 20.7-36.6) of the experimental arm (p NS). Conclusions: From the present study, the first phase II randomized trial testing the addition of a new generation hormone agent to D, DE improved the 6-mo disease control with a prolongation of PFS compared to the standard chemotherapy. Clinical trial information: NCT02453009.