Large Study Adds Clarity to Use of Docetaxel With Standard Care in Advanced, Hormone-Naïve Prostate Cancer

Peter Paul Yu, MD, FACP, FASCO

The addition of docetaxel to standard hormonal therapy significantly improved survival among men with newly diagnosed, hormone-naïve advanced prostate cancer, according to a large study presented in a presscast held ahead of the 2015 ASCO Annual Meeting. These data are part of the STAMPEDE trial, the largest randomized prostate cancer clinical trial ever conducted.

Two other, smaller studies have previously examined the use of docetaxel in this space, with mixed results. In the phase III CHAARTED trial, which was presented at the 2014 ASCO Meeting, it was shown that docetaxel in combination with standard hormone therapy extended overall survival (OS) by nearly 14 months. In the GETUG-15 trial in France, no survival advantage was seen.

“This is a much larger study than previously seen and continues to add increasing evidence that adding chemotherapy early on prolongs survival in men,” Peter Paul Yu, MD, FACP, FASCO, ASCO president, said during the briefing.

OS was approximately 77 months and 67 months for those receiving docetaxel with standard of care (SOC) and SOC alone, respectively (HR = 0.76; 95% CI, 0.63—0.91; P = .003). Further, adding zoledronic acid to SOC with or without docetaxel did not have an effect on survival.

In this portion of STAMPEDE, 2962 patients were randomized 2:1:1:1 to receive SOC, SOC plus docetaxel, SOC plus zoledronic acid, or SOC plus docetaxel and zoledronic acid.

SOC was defined as hormonal therapy for at least 3 years while docetaxel was administered at 75mg/m2 for six 3-weekly cycles with prednisolone 10mg daily. Zoledronic acid was given for six 3-weekly cycles then 4-weekly for 2 years.

The groups were balanced, according to the study’s authors. Median age was 65 years and 93% of patients were diagnosed within 6 months of randomization. In total, 61% of patients had metastatic disease — 22% had no regional lymph node involvement and no distant metastasis while 14% had node-positive disease and distant metastasis that could not be evaluated. Median PSA was 65 ng/mL and men were required to have a Gleason score of at least 8.

Docetaxel in addition to SOC improved survival by 24% (HR = 0.76; 95% CI, 0.63—0.91; P = .003) and failure-free survival by 38% (HR = 0.62) compared with SOC alone. Both were clinically and statistically significant, lead author Nicholas David James, MD, PhD, said.

“Our headline conclusion would be that docetaxel should be considered as routine practice in men with newly diagnosed metastatic disease,” James said. “With non-metastatic disease, there remains uncertainty as to whether there’s a survival benefit or not but it certainly improves failure-free survival by a substantial amount.”

James is the director of the Cancer Research Unit and a professor of clinical oncology at the University of Warwick in Coventry, United Kingdom.

Improvements in OS were also seen in the other 2 arms of the trial, though results were not statistically significant. OS was improved by 7% in the SOC plus zoledronic acid arm (HR = 0.93; 95% CI, 0.79-1.11; P = .437) and 19% in the SOC plus docetaxel plus zoledronic acid arm (HR = 0.81; 95% CI, 0.68-0.97; P = .020).

Rates of toxicity varied between the 4 arms. Grade 3-5 toxicities were seen in 31% of patients in the SOC arm, 50% in the SOC and docetaxel arm, 32% in the SOC and zoledronic acid arm, and 52% in the arm receiving SOC, zoledronic acid, and docetaxel.

Yu said docetaxel is tolerable as single agent and that toxicity should not affect the agent’s expanded use.

“[There is a] very strong hint that this strategy of bringing chemotherapy early on can have a benefit, even in men who do not have evidence of metastases, at the time they’re starting hormone therapy,” Yu said.

The entire STAMPEDE trial includes 9 arms and approximately 7000 patients. In addition to zoledronic acid and docetaxel, celecoxib, abiraterone, and enzalutamide are also being examined in STAMPEDE.

James ND, Sydes, MR, Mason, MD, et al. Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: First overall survival results from STAMPEDE. J Clin Oncol. 2015;(suppl; abstr 5001).

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