784O - Docetaxel (D) with androgen suppression (AS) for high-risk localized prostate cancer (HrPC) patients (pts) who relapsed PSA after radical prostatectomy (RP) and/or radiotherapy (RT): A randomized phase III trial

Abstract

Background: HrPC pts with PSA relapse after local therapy may have a poor prognosis and AS may be a therapeutic option. D+AS is standard of care in hormone-naive metastatic PC. We evaluated the benefit of D+AS in HrPC pts with PSA relapse after RP and/or RT. Methods: Multicenter, randomized phase 3 study (NCT00764166) comparing AS (triptorelin, every 3 months for 1 year) versus AS+D (70 mg/m2 Q3W, 6 cycles). To be enrolled, pts needed ≥ 3 rising PSA values >0.2ng/mL (after RP) or > 1ng/mL above nadir (after RT) modified by nadir + 2ng/ml (RTOG-ASTRO Phoenix, 2006) and ≥ 1 of the following criteria: Gleason ≥8, PSA doubling time (PSADT) ≤6 mths, PSA velocity >0.75 ng/mL/year, positive surgical margins (SM), pN1, time from curative therapy to PSA relapse ≤12 months. Pts were stratified on type of local treatment (RP or RT) and PSADT (≤ or > 6 mths). Primary endpoint was PSA-PFS defined by a PSA above 0.2ng/ml and rise ≥ 50% from baseline confirmed by 2 subsequent values. Secondary endpoints were PSA response (decrease ≥50%), radiological progression (rPFS), overall survival (OS) and safety. Results: between 2003-2007, 250 pts (median age 65 years), were randomized to AS+D (arm A, n = 125) or AS (arm B, n = 125). Local treatment: RP (95 pts, 38%), RT (69 pts, 28%) or RP+RT (86 pts, 34%). Risk factors were as follows: Gleason ≥8: 29%, PSADT≤ 6 mths 54%, PSA velocity >0.75 ng/mL/yr 84%, positive SM 37%, pN1 4%, PSA relapse ≤12 mths 45%. 58% of pts had ≥3 risk factors. Six pts had a PSA >20 ng/ml at baseline. There was no significant difference in PSA response (94% vs 98%), PSA-PFS and rPFS between 2 arms (table). Median OS was not mature. Most common grade ≥3 toxicities in arm A were neutropenia (58%), febrile neutropenia (8%) and hair loss (4%). AS toxicities were mainly grade 2 hot flushes (47%) and depression (11%).Table784OAS + D (n = 125)AS alone (n = 125)HR (95%)p-valuePSA-PFS (months)20.7 [19.2-21.5]18.6 [17.6-20.2]0.85 (0.62-1.16)0.31rPFS (years)8.8 [7.7-10.2]9.7 [6.9-10.9]1.01 (0.72-1.40)0.9525eme percentile (OS, years)8.38.11.16 (0.76-1.77)0.49 Open table in a new tab Conclusions: AS+D failed to improve PSA-PFS, rPFS in HrPC pts relapsing PSA after local therapy. Clinical trial identification: NCT00764166 Legal entity responsible for the study: Stéphane OUDARD, MD, PhD Funding: Sanofi Aventis Disclosure: S. Oudard: Honoraria from Sanofi, Novartis, Roche, Ipsen, BMS outside submited work L. Miglianico, E. Sevin, A-C. Hardy Bessard: Fees from Sanofi. C. Chevreau, C. Linassier, S. Culine: Fees from Sanofi, Astellas, Janssen. F. Priou: Fees from Sanofi. P. Beuzeboc: Fees from Sanofis, Astellas, Janssen. G. Gravis: Travel paid by Sanofi, Astellas, Janssen All other authors have declared no conflicts of interest.