Results from the STAMPEDE trial showed that the addition of docetaxel to standard hormone therapy improved overall survival by a median of 10 months over hormone therapy alone in men with newly diagnosed, advanced, hormone therapy–naive prostate cancer.¹ The study also showed that zoledronic acid added no benefit over standard hormone therapy or standard hormone therapy plus docetaxel.

“Docetaxel improved survival in patients with newly diagnosed metastatic prostate cancer starting hormones, and it should be routinely used in these patients as part of upfront treatment. In nonmetastatic disease, docetaxel should be offered to men about to start hormones for the first time, because it prolongs failure-free survival. There is some uncertainty regarding its effect on overall survival in men with nonmetastatic disease, and longer follow-up is needed. It’s clear that zoledronic acid does not benefit patients with advanced prostate cancer and should not be offered as upfront treatment,” said lead author Nicholas ­David James, MD, PhD, of the University of Warwick in Coventry, United Kingdom, at a press briefing held in advance of the ASCO Annual Meeting, where the new data will be presented (abstract 5001, being presented May 31, 2015).

STAMPEDE is the largest randomized clinical trial conducted to date of treatment for prostate cancer. Since 2005, more than 6,500 men have been enrolled, and the standard of care arm continues to enroll patients. The innovative, multiarm, adaptive design discards ineffective treatments and includes newer effective treatments based on trial results. The study continues to assess newer treatments.

The presentation at the 2015 ASCO Annual Meeting will focus on the first overall survival results in 2,962 hormone-naive men randomized between October 2005 and March 2013 in a 2:1:1:1 ratio to one of four of STAMPEDE’s nine different treatment arms: standard of care, standard of care with docetaxel for six cycles, standard of care with zoledronic acid for 2 years, and standard of care with both docetaxel and zoledronic acid.

In this comparison, standard of care was at least 3 years of androgen-deprivation therapy, with local radiation for suitable patients. About 60% had metastatic disease at enrollment, and 40% had high-risk, locally advanced, nonmetastatic prostate cancer, defined as node-negative, stage T3-4, prostate-specific antigen level ≥ 40 ng/mL, or Gleason score of 8–10.

Overall survival was a median of 10 months longer in the docetaxel arm vs standard of care: 77 months vs 67 months, respectively, reflecting a 24% relative improvement in survival. The magnitude of improved overall survival was even greater when docetaxel was added to hormone therapy in the subset of patients with metastatic disease: 65 months vs 43 months, respectively, a difference of 22 months. In the overall analysis, failure-free survival was improved by 38% with docetaxel.

In an analysis of metastatic vs nonmetastatic disease, metastatic patients had a clinical and statistically significant 37% improvement in survival, but the study was not powered to detect a significant survival benefit in the nonmetastatic group.

The addition of docetaxel to hormone therapy does lead to increased toxicity.

The STAMPEDE data come on the heels of two other trials in this setting, which reported conflicting findings. CHAARTED, a 790-patient U.S. trial, found that docetaxel achieved a significant survival advantage, whereas GETUG-15, a 385-patient French trial, did not [see box]. STAMPEDE is larger than either of these studies, with broader enrollment criteria, and the authors believe that these new results should help clarify the role of docetaxel in newly diagnosed, high-risk cancer.

Additional Commentary

“Considering these results along with the recently reported CHAARTED trial provides further evidence for adding docetaxel to androgen-deprivation therapy as part of the initial therapy for men with metastatic disease,” commented Howard I. Scher, MD, Chief, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York. Dr. Scher noted that at this point, however, it is premature to establish androgen-deprivation therapy and docetaxel as a standard of care for all newly diagnosed patients.

“One consideration is that the benefit was not without cost, as there was a higher frequency of grade 3–5 adverse events in the chemotherapy group. As such, it is important to know the outcome for each of the cohorts evaluated, in terms of both safety and efficacy, so that the potential risk/reward can be estimated and discussed with patients who are considering this approach,” stated Dr. Scher.

“Another consideration is the proportion of men in the androgen deprivation–alone arm who received docetaxel at the time of disease progression. It is necessary to assess whether giving the combination ‘upfront’ is superior to giving hormones first and chemotherapy later,” he said. ■

Disclosure: Dr. James has received honoraria from Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, and Astellas. Dr. Scher has had an advisory role for and received research grants from Sanofi-Aventis.

Reference

1. James ND, et al: 2015 ASCO Annual Meeting. Abstract 5001. To be presented May 31, 2015.