CHICAGO, IL USA (UroToday.com) - Dr. Nicholas James presented the initial survival results from the STAMPEDE study of men with metastatic or biochemical recurrent hormone sensitive prostate cancer. Investigators enrolled men with high-risk, locally advanced or metastatic prostate cancer and treated them with androgen deprivation therapy (ADT) for ≥ 3 years -- with radiation therapy being strongly encouraged for men without nodal or metastatic disease before November 2011, then mandated as standard of care changed. Radiation was optional for men with lymph node involvement. Men were randomized in a complex pattern to receive one or two of three treatment approaches, all with standard of care (SOC, defined as ADT +/- radiation), or SOC alone. In this analysis, only men randomized to docetaxel, zoledronic acid, a combination of the two, or SOC alone were included. The group hypothesized that treatment with docetaxel would be associated with an improvement in survival, that zoledronic acid may be associated with prolonged time to metastatic disease, and that the combination may be the most effective in terms of prolonging overall survival.
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Between October 2005 and March 2013, the investigators recruited 2 962 patients with high risk metastatic or node positive disease, with 1 184 receiving SOC alone, 593 receiving zoledronic acid (4 mg every 3 weeks, up to 18 weeks, then every 4 weeks, up to 2 years), 592 receiving docetaxel (75 mg/m2 once every 3 weeks for 6 cycles), and 593 receiving zoledronic acid plus docetaxel (docetaxel 60 mg/m2 once every 3 weeks for 6 cycles, and zoledronic acid 75 mg/m2 once every 3 weeks for 6 cycles). Median follow up was 42 months. The primary outcome was overall survival (OS), and secondary outcomes included failure-free survival (FFS, defined as any PSA failure, local failure, lymph node failure, distant metastatic failure, or prostate cancer death), toxicity, quality of life, skeletal-related events, and cost effectiveness. The investigators sought to identify a 25 % improvement in overall survival. The median age of the population was 65-years old with more than 75% having a WHO performance status of 0. The majority had metastatic disease (61%), and 85% of these were bone metastases. Approximately 24% had biochemical recurrence only, and 15% had node positive but not metastatic disease. In terms of radiation, 29% were planned for radiation, and 6% had prior local therapy. Men were stratified by hospital and NSAID/aspirin use.
Results were mixed in terms of the effectiveness of various treatments. Zoledronic acid did not significantly prolong FFS as compared to SOC (HR 0.93, 95% CI 0.82 – 1.05, p = 0.26). Docetaxel significantly prolonged FFS as compared to SOC (HR 0.62, 95% CI 0.54 – 0.70, p < 0.001), and was also associated with prolonged OS (HR 0.76, 95% CI 0.63 – 0.91, p = 0.003). This resulted in a 10-month improvement in survival, with a median OS in the docetaxel arm of 77 months vs 67 months in the SOC arm. The docetaxel plus zoledronic acid combination was associated with a similar prolongation in FFS and OS (HR for OS 0.81, 95% CI 0.68 – 0.97, p = 0.02). The investigators performed multiple pre-planned subgroup analyses, including metastatic status, nodal status, Gleason sum score, PSA pre-treatment, age at randomization, WHO performance status, and NSAID/aspirin use. When assessing OS by metastatic status, they found that men with metastatic disease appeared to have a significant benefit from treatment with docetaxel, while men with biochemical recurrence only did not, though the study was underpowered to assess OS in men with biochemical recurrence. The OS benefit of docetaxel was present in both the docetaxel alone and docetaxel plus zoledronic acid arms as compared with men treated with SOC alone. For men with metastatic disease, median overall survival was 65 months with docetaxel vs 43 months with SOC alone, p = 0.002. There did appear to be good access for men in the SOC arm to receive treatment with additional disease modifying therapies.
In the end, docetaxel was associated with an improvement in overall survival for men with hormone-naïve prostate cancer. Men with metastatic disease and biochemical recurrence were included in the analysis, but the analysis was only powered to detect a clear benefit from docetaxel in the metastatic setting, and was underpowered to assess OS differences between treatment arms in the biochemical recurrent setting. Zoledronic acid is not associated with a survival benefit in this setting. The combination of zoledronic acid and docetaxel is associated with improved OS, but the addition of zoledronic acid does not appear to confer a benefit over docetaxel alone.
Presented by Nicholas James at the American Society of Clinical Oncology (ASCO) Annual Meeting - Illumination & Innovation: Transforming Data into Learning - May 29 - June 2, 2015 - Chicago, Illinois USA
University of Warwick, Coventry, UK
Reported by Alicia K. Morgans, MD, assistant professor of medicine and medical oncologist at Vanderbilt-Ingram Cancer Center, and medical writer for UroToday.com