Phase III study of addition of docetaxel (D) to hormonal therapy (HT) versus HT alone in nonmetastatic high-risk prostate cancer (PC) patients (pts): Final results on PSA progression-free survival

Abstract

4523 Background: Around 75% of nonmetastatic high risk PC pts undergo PSA recurrence within 2 years after local therapy. Activity of D in addition to HT was investigated in this population. Methods: A multicenter, randomized phase III study was designed to compare A: HT+D (70 mg/m2 Q3W, 6 cycles) and B: HT (triptorelin, every 3 months (m) for 1 year in non-metastatic PC pts at high-risk of recurrence after radical prostatectomy (RP) and/or radiotherapy (RT). Stratification factors (SF): RP vs RT and PSA-DT < or > 6m. Inclusion criteria were at least 1 of: Gleason > 8, PSA-DT < 6m, positive surgical margins, PSA velocity > 0.75ng/mL/year, pathological pelvic lymph nodes, time from RP/RT to inclusion < 12m. Within 90 days before inclusion, at least 3 consecutive progressive PSA > 0.2ng/mL (RP) or > 1ng/mL (RT). Primary endpoint was PSA PFS; secondary endpoints were PSA response, time to metastasis, overall survival, QoL and safety (NCI-CTC 2.0). Progression definition: not-responding pts, 25% PSA increase above baseline; responding pts, PSA increase > 25% above nadir (3 values) above 0.1ng/mL with absolute increase (AI); no definition of AI is available for PSA progression in this setting, therefore AI was incremented from 0.2 to 2.0ng/mL by 0.1 step. We also investigated a definition with 50% PSA increase. Multivariate analysis: Cox regression model adjusted on SF. Results: Included =254, ITT=251. Arm A (125) vs B (126): median age(y) 64 vs 66, time(m) initial diagnosis to inclusion 35 vs 34, ECOG=0 96% vs 93%, Gleason score (%) > 8 32 vs 27, RP (%) 69.6 vs 71.4, RT (%) 37.6 vs 38.1, PSA-DT (%) < 6m 53.6 vs 53.2, respectively. PSA response (%pts) in A vs B was: CR=74 vs 64, PR=21 vs 32, SD=4 vs 3. Toxicity was reported at ASCO 2010 (Abstract 4685). Upon variation of AI, Hazard Ratio A vs B spread between 0.74 and 0.91 (p<0.05 for AI=0.8-0.9ng/mL). Therefore, whatever the AI, a risk reduction was observed in arm A vs B. Results were identical at 25% or 50% increase above nadir. Conclusions: Addition of docetaxel to hormonotherapy at an early stage in nonmetastatic high-risk PC patients reduces risk of PSA relapse by 9-26%. Clinical PFS monitoring is ongoing.