Docetaxel should be considered routine therapy in men with metastatic prostate cancer, according to data to be presented at the American Society of Clinical Oncology Annual Meeting (Abstract 5001). The study, discussed in a teleconference for reporters in advance of the meeting, showed that the drug extends survival in previously untreated patients starting hormone treatment for the first time.
The report represents the first survival results from the STAMPEDE trial, with study arms comparing standard of care (hormone therapy with radiotherapy in some cases), docetaxel, zoledronic acid, and docetaxel with zoledronic acid.
Survival results for men with non-metastatic disease were not as clear, but since docetaxel did increase failure-free survival by a significant amount it should be considered for selected men with non-metastatic high-risk disease, said the study's lead author, Nicholas James, MD, Director of the Cancer Research Unit at the University of Warwick and Consultant in Clinical Oncology at Queen Elizabeth Hospital.
The study also showed that zoledronic acid alone did not extend survival for these patients. And while treatment with both zoledronic acid and docetaxel did improve survival, James reported, it did not offer any benefits compared with docetaxel alone.
STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) is an ongoing randomized controlled trial using a multi-arm multi-stage design. Approximately 7,000 men with high-risk locally advanced or metastatic prostate cancer were recruited, who were starting long-term hormone therapy for the first time. The trial initially assessed adding one or two of three treatment approaches to standard of care.
This report involved the primary survival results for 2,962 men randomly selected to receive one of four regimens:
- Standard of care alone (androgen deprivation therapy, and in some cases with radiotherapy);
- Standard of care with docetaxel;
- Standard of care with zoledronic acid; and
- Standard of care with a combination of the two.
James said the rationale for combining docetaxel and zoledronic acid was because there is in-vitro evidence of synergy.
Men with locally advanced prostate cancer starting long-term hormone therapy for the first time for high-risk disease were enrolled if they fell into any of four categories:
- Locally advanced with two of three factors: T3/T4 tumor, PSA over 40 ng/mL, or Gleason score of 8 or higher;
- Lymph-node positive disease;
- Metastatic disease; or
- Aggressive relapse post-surgery or post-radiotherapy, defined as either a rapid rise in prostate-specific antigen or a PSA level higher than 20 ng/mL.
Approximately 60 percent of the men enrolled had metastatic disease, seven percent had aggressive relapse, and 33 percent had either locally advanced disease or lymph node positivity.
Docetaxel is licensed for treatment of relapsed prostate cancer and produces a survival advantage of about three months, James said.
With seven years of follow-up, hormone therapy plus docetaxel produced a 24 percent relative improvement in overall survival compared with standard of care, he reported. That represented a failure-free survival time of 77 months for the docetaxel arm versus 67 months for standard of care alone.
For men with metastatic disease the improvement in overall survival was higher—65 months for the docetaxel arm versus 43 months for standard of care.
Docetaxel also extended the time to relapse by 38 percent in all patients.
The results for docetaxel plus zoledronic acid were essentially similar, James said. “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. But zoledronic acid does not benefit these patients and should not be offered as an upfront treatment for advanced prostate cancer.”
‘Decades of Bias Toward Hormone Therapy Alone’
ASCO 2014-2015 President Peter Paul Yu, MD, Director of Cancer Research at Palo Alto Medical Foundation, put the study in the broader context of treating men who are usually elderly when diagnosed with prostate cancer.
He said the paradigm for decades has been to treat these men with hormone therapy because it is relatively less toxic than chemotherapy, although it does have significant side effects.
“The bias has been to use hormone therapy until there is no response left and then, at the last moment, use chemotherapy, which is essentially a self-defeating strategy because the chemotherapy is started when the disease has evolved to a much more aggressive point.”
Yu said that evidence was presented at last year's ASCO Annual Meeting from the CHAARTED trial showing that this might be the wrong strategy, and that giving chemotherapy early-on and upfront along with hormone therapy might be better than sequentially giving hormone therapy and then chemotherapy.
“STAMPEDE is a much larger study than we have previously seen, and it adds to increasing evidence that using chemotherapy early on prolongs survival in men,” Yu said. “This paradigm shift is continuing and should be highlighted.”
He added that in the trial there is a strong hint that this strategy of bringing in chemotherapy early on can have a benefit even in men who do not have evidence of metastases at the time they start hormone therapy—in other words, the adjuvant use of chemotherapy.