ASCO 2015: Adding Chemotherapy to Initial Therapy Improves Survival in Patients With Advanced, Hormone-Naive Prostate Cancer
- Docetaxel plus standard therapy improved overall survival by an average of 10 months in men with newly diagnosed, hormone-naive, advanced prostate cancer.
- For the subset of patients with metastatic disease, the average improvement in overall survival was even higher, 22 months.
- Adding zoledronic acid (BLOCKS LOSS OF CALCIUM IN WOMEN WITH OSTEOPOROSIS HOPED TO IN MEN 0NOT SHOWN) to standard therapy did not affect survival, and adding the combination of zoledronic acid and docetaxel was not more effective than adding just docetaxel.
The UK-led STAMPEDE trial found that adding docetaxel chemotherapy to standard hormone therapy markedly improved survival for men with newly diagnosed advanced prostate cancer not previously treated with hormone therapy (hormone-naive). Men who received docetaxel plus standard therapy lived on average 10 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. These findings were presented today at a presscast in advance of the 2015 ASCO Annual Meeting (Abstract 5001).
“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, nonmetastatic 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. “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 is the largest randomized 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 multistage, multiarm design that can be modified both to assess new therapies and adapt to changes in the standard of care. The standard of care in the continuously recruiting control arm changes 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 ineffective are stopped, and new arms are added to assess the efficacy of emerging treatments, such as novel hormone drugs.
At the 2015 ASCO Annual Meeting, researchers will be reporting results on 2,962 hormone-naive men who were assigned to 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. The standard of care was at least 3 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 nonmetastatic prostate cancer (node-negative, stage T3/4, prostate-specific antigen level ≥ 40 ng/mL or Gleason sum score 8–10).
After a median follow-up of 42 months, 948 men had died. Overall survival was on average 10 months longer in the docetaxel arm compared with the standard of care 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). It is important to note that docetaxel also extended the time to relapse by 38% in all patients.
Although docetaxel was associated with some additional toxicity compared with standard of care alone, the side effects were manageable, and 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 standard of care and the standard of care plus zoledronic acid. The addition of zoledronic acid to the combination of standard of care and docetaxel yielded similar outcomes as standard of care with only docetaxel.
Two previous, smaller trials have reported results on using docetaxel in the hormone-naive metastatic setting. These trials showed conflicting results. CHAARTED, a United States–based trial reported in the plenary session of the 2014 ASCO Annual Meeting, showed a survival advantage; GETUG-AFU 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 the previous two trials, comprising men with metastatic prostate cancer and 600 men with locally advanced, nonmetastatic disease.
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, nonmetastatic prostate cancer, given the reduction in risk of relapse seen in this study. However, longer follow-up is needed to determine whether there is any survival advantage in men with nonmetastatic disease.
This study was supported by Cancer Research UK, UK Medical Research Council, the UK National Cancer Research Institute, the UK Department of Health, Sanofi-Aventis, Novartis, Pfizer, Janssen, and Astellas.