Phase 3 Randomized Controlled Trial of Androgen Deprivation Therapy with or Without Docetaxel in High-risk Biochemically Recurrent Prostate Cancer After Surgery (TAX3503).

Abstract Background No standard of care exists for patients with high-risk biochemical recurrence (BCR) after prostatectomy. Objective To evaluate whether addition of docetaxel to androgen deprivation therapy (ADT) improved progression-free survival (PFS) in high-risk BCR patients. Design, setting, and participants TAX3503 was a multicenter phase 3 trial that randomized patients with high-risk BCR to ADT for 18 mo ± docetaxel (75 mg/m2 q3w for ten cycles). Eligibility included prostate-specific antigen (PSA) ≥1.0 ng/ml after prostatectomy alone or after postoperative radiation therapy, PSA doubling time ≤9 mo, and absence of metastases on computed tomography and bone scintigraphy. Outcome measurements and statistical analysis The primary endpoint was PFS following testosterone recovery to noncastrate levels (testosterone >50 ng/dl). Secondary endpoints included time to testosterone recovery, overall survival (OS), quality of life, and safety. Results and limitations Between September 2007 and May 2011, 413 patients were assigned to ADT ± docetaxel. In 2012, following completion of accrual and treatment, the sponsor withdrew support of the study, and in 2013, a registry was created to secure the primary endpoint. The final analysis included data from the original trial and registry. At a median follow-up of 33.6 mo, 260 patients demonstrated testosterone recovery, which occurred similarly between groups. ADT plus docetaxel trended toward a nonclinically meaningful improvement in PFS (median 26.2 vs 24.7 mo) for the testosterone-recovered population (218 events, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61–1.04) and in OS for the intention-to-treat population (medians not reached, HR 0.51, 95% CI 0.23–1.10). Grade ≥3 adverse events occurred more frequently in the ADT plus docetaxel group (48.0% vs 10.8%). Conclusions TAX3503 did not demonstrate a meaningful benefit of adding docetaxel to ADT in patients with high-risk BCR. Testosterone recovery was unaffected by addition of docetaxel to ADT. Patient summary Addition of docetaxel to androgen deprivation therapy did not meaningfully improve outcomes for men with high-risk biochemically recurrent prostate cancer.