The UK-led trial STAMPEDE found that adding docetaxel chemotherapy to standard hormone therapy markedly improves survival for men with newly diagnosed advanced prostate cancer not previously treated with hormone therapy (hormone- naïve).

Men who received docetaxel plus standard therapy lived on average ten months longer than those who received only standard therapy.

In contrast, adding zoledronic acid to standard therapy did not affect survival, and adding the combination of zoledronic acid and docetaxel was not more effective than adding just docetaxel.

“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,” said 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.

“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.”

STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy), is the largest randomised clinical trial of treatment for men with prostate cancer ever conducted, with more than 6,500 patients enrolled since 2005.

The ongoing study has an innovative multi-stage, multi-arm design, which was developed with and run from the Medical Research Council Clinical Trials Unit at University College London.

The trial can be modified to both assess new therapies and adapt to changes in the standard of care.

The standard of care (SOC) in the continuously recruiting control arm can change as treatment patterns change.

For example, radiation therapy has been added to the mainstay androgen deprivation therapy for certain patients.

As the trial goes on, treatment arms that are found to be insufficiently active are stopped, and new arms are added to assess the efficacy of emerging treatments, such as novel hormone drugs.

At ASCO’s Annual Meeting, researchers will be reporting results on 2,962 hormone-naïve men who were assigned to four of STAMPEDE’s nine different treatment arms: SOC, SOC with docetaxel for six cycles, SOC with zoledronic acid for two years, and SOC with both docetaxel and zoledronic acid.

The SOC was at least three years of androgen deprivation therapy, with local radiation for suitable patients.

About 60% of the patients had metastatic disease when joining the trial and the rest had high-risk, locally advanced non-metastatic prostate cancer (either node-positive, or with 2 of 3 risk factors: stage T3/4, PSA≥40ng/ml or Gleason sum score 8-10).

After a median follow-up of 42 months, 948 men had died.

Overall survival was on average ten months longer in the docetaxel arm compared to the SOC arm (67 vs. 77 months) with a relative improvement of 24%.

For the subset of patients with metastatic disease, the average improvement in overall survival was even higher, 22 months (from 43 vs. 65 months).

Importantly, docetaxel also extended the time to relapse by 38% in all patients.

Two previous, smaller trials have reported results on using docetaxel in the hormone-naïve metastatic setting.

These trials showed conflicting results. CHAARTED in the USA reported in the plenary session of ASCO 2014 showed a survival advantage; GETUG-15 in France did not.

STAMPEDE goes a long way in clarifying the role of docetaxel in men with newly diagnosed, high-risk prostate cancer.

The trial also included a larger and broader patient population than those trials, comprising around 1800 men with metastatic and 1200 high-risk non-metastatic prostate cancer.

According to the authors, the overall findings of this study suggest that men with newly diagnosed metastatic prostate cancer should be offered docetaxel as part of their initial therapy.

They suggest that doctors may also discuss the option of adding docetaxel with patients who have advanced, non-metastatic prostate cancer, given the reduction in risk of relapse seen in this study.

However, longer follow-up is needed to determine if there is any survival advantage in men with non-metastatic disease.

While docetaxel was associated with some additional toxicity compared to SOC alone, the side effects were manageable, and very few patients discontinued docetaxel due to side effects.

Results of a quality of life analysis will be reported at a later time.

The difference in survival was not statistically significant between the SOC and SOC plus zoledronic acid arm.

Addition of zoledronic acid to the combination of SOC and docetaxel yielded similar outcomes as SOC with only docetaxel.

Source: ASCO