Docetaxel-Estramustine In High-Risk Localized Prostate Cancer: First Results Of The French Genitourinary Tumor Group Phase Iii Trial (Getug 12).

4513 Background: Docetaxel improves survival in patients (pts) with castrate-resistant prostate cancer (CaP). This phase III trial assessed docetaxel-based chemotherapy in pts with high-risk localized CaP. Methods: Eligibility included non-pretreated high-risk localized CaP (defined as ≥1 of the following criteria: T3-T4, Gleason score (GS) ≥8, PSA ≥ 20 ng/mL, pN+). All pts had a staging pelvic lymph node dissection. This prospective, randomized trial was stratified on the four above-mentioned prognostic factors. Pts were randomly assigned to either goserelin 10.8 mg every 3 months for 3 years and 4 cycles of docetaxel 70 mg/m2 q3w + estramustine 10 mg/kg/d d1-5 (DE arm) or goserelin alone (H arm). Local therapy was administered at 3 months. The primary endpoint was progression-free survival (PFS). The hypothesis was based on an expected 70% 4-year PFS rate in the control arm. The planned number of pts was 400, to detect a 12% difference with a power of 80% and a type I error of 0.05 (two-sided Logrank Test). Results: 413 pts were accrued (207 DE arm, 206 H arm): T3-T4 (67%), GS ≥8 (42%), PSA > 20 ng/mL (59%), pN+ (29%). Local treatment consisted of radiotherapy in 358 pts (87%) (median dose 74 Gy). All characteristics were well balanced. 94% of the pts received the planned 4 cycles of docetaxel. Toxicity included grade 3-4 neutropenia (27%) with neutropenic fever in 2%. There was no toxicity-related death and no secondary leukemia. After 3 months of systemic treatment, the PSA response rate defined as a serum PSA ≤ 0.2 ng/mL was 34% in the DE arm vs 15% in the H arm (p< 0.0001). With a median follow-up of 4.6 years, the 4-year PFS rate is 85% [79–89] in the DE arm vs 81% [75–86] in the H arm. The adjusted hazard ratio for PFS between the two arms is 0.79 [0.53-1.18], (p=0.26). With a total of 44 deaths, the 4-year overall survival rate is 94% [91–96]. Conclusions: Docetaxel-estramustine can be safely combined with standard therapy in high-risk localized CaP and significantly improves the PSA response rate. With a lower than expected number of events in both arms, the observed difference in 4-year PFS did not reach significance. A longer follow-up is required.