Genitourinary tumors, prostate

ABSTRACT Background Androgen deprivation therapy (ADT) is the standard treatment of hormone-sensitive metastatic prostate cancer (HSMPC). We performed a phase III multicentre trial to compare ADT alone with ADT plus docetaxel (D) in HNMPC. Methods Patients (pts) with HSMPC were randomly assigned to either arm A (ADT + D: 75mg/m q3w, up to 9 cycles) or arm B (ADT). The primary endpoint was overall survival (OS). The planned number of pts was 378 to detect an improvement in OS with a hazard ratio (HR) of 0.62, a power of 80% and an alpha risk of 0.05 (two-sided test). Secondary endpoints were biological progression-free survival (PFS) and clinical PFS. Data on toxicity and quality of life have been previously presented. Results From October 2004 to December 2008, 385pts were included. Baseline characteristics were well balanced between the two arms. Median age was 63 years (43-84), median PSA was 26.4 ng/ml (0.1-11900), Gleason score was ≥ 8 in 57%. Prognostic classification was as follows: good prognosis (49%), intermediate (29%) and poor (22%). The majority of pts had metastases at the time of diagnosis (72%), 28% developed metastases after local treatment failure. Median number of D cycles was 8 (range 0-9). The median follow-up was 50 months (mo) [95%CI: 49-54]. At 6 mo, a higher PSA response (≥ 50%) in arm A (94% vs 85%, p = 0.0096) and a higher PSA progression (≥ 25%) in arm B (10% vs 1%, p = 0.0015) were observed. Biological PFS was significantly longer in arm A: 22.9 vs 12.9 mo, HR; 0.72 [95%CI: 0.57-0.91] (p = 0.005). Clinical PFS was increase in arm A: 23.46 vs 15.44 mo, HR: 0.75 [95CI: 0.59-0.94] (0.015). OS was not significantly different (median: 58.9 mo in arm A and 54.2 mo in arm B, HR: 1.01 [95%CI: 0.75-1.36]. The median OS for each prognostic group was 69.1 [95%CI: 60.9-NR], 46.5 [95%CI: 37.7-NR] and 36.6 [95%CI9: 28.5-58.9] mo respectively in the good, intermediate, and poor prognosis groups (p = 0.001), with no difference between the two arms. At the cut-off time, 65% of pts from the ADT arm had received docetaxel since they developed castrate-resistant prostate cancer. Conclusion Combining docetaxel and ADT improves PFS over ADT alone in pts with HSMPC. However, no difference in OS was observed between the two arms. Disclosure G. Gravis: I have expert testimony to disclose: Sanofi Aventis, uncompensated. K. Fizazi: Participation to advisory boards and speaker for Sanofi-Aventis. F. Joly Lobbedez: advisory board/board of directors position: Sanofi, Roche, Pfizer, Novartis, Ferring; compensated consultant relationship: Roche, Novartis; honoraria: Sanofi, Roche, Pfizer, Novartis, Ferring, Ipsen,Takeda; travel remuneration: ASCO by Novartis, ESMO by Janssen. S. Oudard: I have an advisory relationship and honoraria to disclose: Pfizer Oncology, Bayer-Schering Pharma, Hoffman La Roche, Glaxo SmithKline, Novartis Pharma, Sanofi Aventis. D. Pouessel: Consultant role and honoraria: Sanofi, P. Beuzeboc: Presentations: Avantis, All other authors have declared no conflicts of interest.