In a phase III trial reported in the Journal of Clinical Oncology, Anthony V. D’Amico, MD, PhD, and colleagues found that the addition of docetaxel to radiotherapy and androgen-deprivation therapy (ADT) did not improve overall survival in nonmetastatic, unfavorable-risk prostate cancer. However, patients receiving docetaxel had a reduced incidence of radiotherapy-induced cancers, and a potential survival benefit was observed among those with a prostate-specific antigen (PSA) level < 4 ng/mL, reflecting a reduction in prostate cancer–specific mortality.
Anthony V. D’Amico, MD, PhD
As stated by the investigators, “Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer, given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.”
The investigator-initiated study included 350 men with T1c-4N0M0 unfavorable-risk disease from sites in the United States, Australia, and New Zealand. They were randomly assigned between September 2005 and January 2015 to receive 6 months of radiotherapy and ADT with (n = 175) or without (n = 175) docetaxel at 60 mg/m2 once every 3 weeks for three cycles before radiotherapy and 20 mg/m2 once weekly during radiotherapy.
The current report includes analyses of the primary endpoint of overall survival, incidence of radiotherapy-induced cancers, and treatment effect on overall survival according to PSA subgroups.
After a median follow-up of 10.2 years, 89 men (25.4%) had died (44 in docetaxel group vs 45 in control group); of these, 42 (47.2%) died from prostate cancer (22 vs 20). The hazard ratio for overall survival for the docetaxel vs control group was 0.99 (95% confidence interval [CI] = 0.65–1.51, P = .98), with 10-year estimates of 72% (95% CI = 63%–79%) vs 74% (95% CI = 66%–80%). Restricted mean survival time over 10 years was 9.11 vs 8.82 years (difference = 0.29%, 95% CI = –0.19 to 0.76, P = .22).
Radiotherapy-induced cancers occurred in one patient in the docetaxel group vs eight in the control group (including 4 fatalities), yielding an age-adjusted hazard ratio of 0.13 (95% CI = 0.02–0.97, P = .046). The 10-year cumulative incidence estimates were 0.61% (95% CI = 0.06%–3.09%) vs 4.90% (95% CI = 2.13%–9.40%), yielding an observed difference of 4.29% (95% CI = 0.51%–8.07%).
In analysis adjusting for age, percent biopsies, Gleason score, and tumor category, the adjusted hazard ratio for overall survival among the docetaxel group vs control group patients with PSA < 4 ng/mL (n = 27) was 0.27 (95% CI = 0.05–1.34), whereas the adjusted hazard ratio among men with a PSA of 4 to 20 ng/mL was 1.51 (95% CI = 0.86–2.67), with P = .05 for the interaction. The improved overall survival among men with PSA < 4 ng/mL was driven by lower prostate cancer–specific mortality in the docetaxel group (0 of 14 patients = 0%) vs the control group (4 of 14 patients = 28.6%).
The investigators concluded, “Adding docetaxel to ADT and radiotherapy did not prolong overall survival in men with unfavorable-risk prostate cancer, but decreased radiotherapy-induced cancer incidence, and may prolong overall survival in the subgroup of men with a PSA < 4 ng/mL by reducing prostate cancer–specific mortality.”
Dr. D’Amico, of the Department of Radiation Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Sanofi and AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.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®.