Addition of Docetaxel to Hormone Therapy in High-Risk Prostate Cancer With Rising PSA Levels
In a French phase III trial reported in JAMA Oncology, Oudard et al 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.
Study Details
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 > 0.2ng/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.
PSA Progression-Free Survival
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).
Adverse Events
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.”
Stéphane Oudard, MD, PhD, of Georges Pompidou Hospital, Paris, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Sanofi and Ipsen. The study authors' full disclosures can be found at jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
