Adding Chemo to ADT Shows Survival Advantage in Second Large Prostate Cancer Study

Nicholas David James, MD, PhD

Adding docetaxel to standard androgen deprivation therapy (ADT) significantly improved overall survival (OS) in men with newly diagnosed, hormone-naive advanced prostate cancer, according to data from the STAMPEDE trial presented in a presscast held ahead of the 2015 ASCO Annual Meeting.

The 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. For ADT plus docetaxel, OS was approximately 77 months compared with 67 months for those treated with ADT alone (HR = 0.76; 95% CI, 0.63—0.91;P= .003). Further, adding zoledronic acid to ADT with or without docetaxel did not have an effect on survival. The remaining arms of the study are still under investigation.

We hope our findings will encourage doctors to offer docetaxel to men newly diagnosed with metastatic prostate cancer, if they are healthy enough for chemotherapy. Men with locally advanced, non-metastatic prostate cancer may also consider docetaxel as part of upfront therapy, as it clearly delays relapse, lead study author Nicholas David James, MD, PhD, director of the Cancer Research Unit at the University of Warwick and Consultant in Clinical Oncology at Queen Elizabeth Hospital Birmingham, United Kingdom, said in a statement. It's also clear that zoledronic acid does not benefit these patients and should not be offered as an upfront treatment for advanced prostate cancer.

In the chemo plus ADT portion of the STAMPEDE study, 2962 patients were randomized 2:1:1:1 to receive ADT, ADT plus docetaxel, ADT plus zoledronic acid, or ADT plus docetaxel and zoledronic acid. ADT 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 ADT 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 ADT alone. Both were clinically and statistically significant, James said.

Our headline conclusion would be that docetaxel should be considered as routine practice in men with newly diagnosed metastatic disease, he noted. 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.

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 ADT plus zoledronic acid arm (HR = 0.93; 95% CI, 0.79-1.11;P= .437) and 19% in the ADT 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 ADT arm, 50% in the ADT and docetaxel arm, 32% in the ADT and zoledronic acid arm, and 52% in the arm receiving ADT, zoledronic acid, and docetaxel.

[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, Peter Paul Yu, MD, FACP, FASCO, ASCO president, said during the briefing.

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, Yu added.

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

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