Stéphane Oudard, MD, PhD
In a French phase III trial reported in JAMA Oncology, Stéphane Oudard, MD, PhD, of Hôpital Européen Georges Pompidou, and colleagues found that the addition of docetaxel to androgen-deprivation therapy (ADT) did not improve prostate-specific antigen (PSA) progression-free survival in men with high-risk prostate cancer with rising PSA after primary local therapy.
In the open-label trial, 254 patients from 28 sites in France were randomly assigned between June 2003 and September 2007 to receive 1 year of ADT plus docetaxel at 70 mg/m2 every 3 weeks for six cycles (n = 127), or 1 year of ADT alone (n = 127). Randomization was stratified by prior therapy and PSA doubling time. Patients had to have high-risk factors, but no current evidence of metastatic disease. Patients had to have three consecutive PSA measurements > 0.2 ng/mL for those who underwent radical prostatectomy and > 1 ng/mL above the nadir for those who received radiotherapy, with the threshold modified to ≥ 2ng/mL in 2006.
The primary outcome measure was PSA progression-free survival, with PSA progression defined as a ≥ 50% relative increase above PSA nadir accompanied by an absolute increase of 0.2 ng/ mL, with confirmation on two additional measurements at 3-week intervals. Final follow-up was in April 2017.
At median follow-up of 30.0 months, median PSA progression-free survival was 20.3 months in the ADT plus docetaxel group vs 19.3 months in the ADT group (hazard ratio [HR] = 0.85, P = .31). At median follow-up of 10.5 years, median time to radiologic progression adjusted for stratification factors was 8.9 years vs 9.0 years (HR = 1.03, P = .88). Median overall survival was not reached in either group. The 25th percentiles for overall survival were 8.7 vs 7.8 years (HR = 0.86, P = .49).
The most common grade 3 or 4 hematologic adverse events in the ADT plus docetaxel group were neutropenia (48.0%), febrile neutropenia (8.0%), and thrombocytopenia (3.0%). No significant differences between groups were observed in quality of life assessed by the EORTC-QLQ-C30.
The investigators concluded: “Compared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA [progression-free survival] in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease.”