In findings from the STAMPEDE trial, a trial that has enrolled more than 9000 men with M0 and M1 prostate cancer since 2005, the addition of docetaxel (Taxotere) to frontline long-term hormone therapy improved quality of life and reduced the need for subsequent therapy in patients with advanced prostate cancer. This has led to lower overall costs in the nonmestatic setting.
Nicholas D. James, MD, PhD
Nicholas D. James, MD, PhD
In findings from the STAMPEDE trial, a trial that has enrolled more than 9000 men with M0 and M1 prostate cancer since 2005, the addition of docetaxel (Taxotere) to frontline long-term hormone therapy improved quality of life and reduced the need for subsequent therapy in patients with advanced prostate cancer. This has led to lower overall costs in the nonmestatic (M0) setting.
“We already knew that docetaxel prolongs survival for men with metastatic (M1) prostate cancer, but this improvement in quality of life and reduction in subsequent treatment, and therefore costs, in M0 disease is somewhat surprising and may cause clinicians to rethink how and when they use docetaxel to treat prostate cancer,” said lead study author Nicholas D. James, MD, PhD, ahead of the 2018 ASCO Genitourinary Cancers Symposium. The data are scheduled to be presented during the meeting in San Francisco, California.
The STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) has evaluated almost a dozen different drugs for treatment of the disease. Results issued in 2016 showed that the 592 men who received docetaxel lived an average of 10 months longer than men on standard therapy. The results released today concerned quality of life and health economics findings from the addition of docetaxel to hormone therapy, compared to hormone therapy as standalone care.
“For those men with prostate cancer that had not metastasized, adding docetaxel to hormone therapy reduced the risk for recurrence by 40%, which both improves quality of life and saves cost for treating cancer recurrence,” James said.
Docetaxel (75 mg/m2) was administered alongside enzalutamide (Xtandi) and abiraterone acetate (Zytiga), the standard of care, for six 3-week cycles with 10 mg of prednisolone daily. Investigators calculated lifetime predictions for cost, changes in predicted survival duration, quality adjusted life years (QALY), and incremental cost effectiveness ratios (ICERs). A QALY was defined as a year of perfect health.
For men with M1 disease that had spread to organs outside of the pelvis, predicted survival was 0.89 years longer compared with men who received only hormone therapy, and the quality of life was preserved 0.51 years longer with the docetaxel combination versus standard of care alone. Those with M0 disease had a predicted survival of 0.78 years and, for them, QALY was preserved for an additional 0.39 years with docetaxel.
James said investigators struggled with how to define a QALY because some patients are willing to tolerate a degree of suffering in order to reach personal goals, such as living long enough to see a grandchild born. Patients were willing to withstand a degree of nausea and fatigue from their treatment. “It is clear that avoiding or delaying recurrence outweighs the upfront toxicity of chemotherapy and adds enough to overall quality of life so that using docetaxel is beneficial,” James said. Investigators noted that QALY gains in M0 patients were driven by the beneficial effect of delayed and reduced relapse.
Investigators stated that in the M0 setting, docetaxel plus standard of care resulted in relatively modest increases in drug costfor docetaxel and management therapy—and lower costs for end-of-life care, adverse events, monitoring, and other life-prolonging therapies. These factors resulted in a slight decrease in costs over standard of care alone. Among patients with M1 disease, docetaxel resulted in a net treatment cost increase of $4200 in the United Kingdom study.
A self-reporting tool was used by participants to rate their health, including mobility, how well they could care for themselves, ability to perform ordinary daily activities, pain and discomfort, and anxiety and depression. These findings enabled investigators to model changes in predicted length of survival, QALY, and incremental cost effectiveness based on the cost benefit of a medical treatment.
The use of docetaxel, with a concomitant 40% reduction in symptomatic skeletal events in both M0 and M1 groups, contributed to an improvement in QALY that was almost fully compensated for by the health setbacks imposed by upfront chemotherapy, “giving you a net gain that is almost as big in M0 men as in M1 patientsand we think this is an extremely important finding,” James said. “Not having a fracture or radiotherapy or spinal cord compression improves your quality of life.”
In the United Kingdom, docetaxel is mandated for use by the National Health Service, but in the United States, oncologists have the choice of using abiraterone acetate or docetaxel. In the UK, the annual cost of docetaxel is $6750 comapred with $33,706 for abiraterone. Investigators concluded that adding docetaxel to standard-of-care treatment was found to be cost effective for both M0 and M1 disease. They said cost savings could potentially be higher in the United States because of the higher costs of treatment here.
James noted it has previously been shown that docetaxel in the M1 setting results in a 40% failure-free survival gain, contrasted with a 25% overall survival gain. “So, extensions to failure-free survival do not translate fully to extensions in survival gain,” he said. In high risk, M0 disease, docetaxel improves failure-free survival by 40% but no fully powered data on overall survival are yet available.
Abiraterone acetate, an oral steroid synthesis inhibitor approved by the FDA in 2011, is among several newer drugs that have come on the market since STAMPEDE began. Abiraterone also has been tested in STAMPEDE, and investigators plan to report the cost effectiveness and quality of life measures for this drug later this year.
It was noted at the conference that although abiraterone acetate may have the benefit of improved tolerability over a short course for chemotherapy, it does does require a much more extensive duration of use and does demand intake of concomitant prednisone, a steroid. Further studies on the cost and quality of life of associated with abiraterone acetate in this setting may help adjudicate selecting either this drug or docetaxel, presenters said.
James N, Woods B, Sideris E, et al. Addition of docetaxel to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Long-term survival, quality-adjusted survival, and cost-effectiveness analysis.J Clin Oncol. 2018;36 (suppl 6S; abstr 162).