1. Fuerst, Mark L.

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SAN FRANCISCO-Adding the chemotherapy drug docetaxel to hormone therapy for advanced prostate cancer improves quality of life, lowers the need for subsequent therapy, and is cost-effective, according to a new study.

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"For those men with prostate cancer that had not metastasized, adding docetaxel to hormone therapy reduced the risk for recurrence by 40 percent, which both improves quality of life and saves cost for treating cancer recurrence," said lead author Nicholas D. James, MD, PhD, Professor of Clinical Oncology at the University of Birmingham, U.K., at a presscast ahead of the 2018 Genitourinary Cancers Symposium (Abstract 162).


"We already knew that docetaxel prolongs survival for men with metastatic prostate cancer, but this improvement in quality of life and reduction in subsequent treatment, and therefore costs, in non-metastatic disease is somewhat surprising and may cause clinicians to rethink how and when they use docetaxel to treat prostate cancer."


Docetaxel improves overall survival by 25 percent in metastatic disease. In high-risk, non-metastatic disease, docetaxel also improves failure-free survival by 40 percent. However, there has been no fully powered, mature data on the effect on overall survival in patients with non-metastatic disease, James noted. Docetaxel also reduces symptomatic skeletal events by around 40 percent in both groups, he added.


STAMPEDE Trial Specifics

Both groups were included in the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trial, which has now enrolled more than 9,000 men with advanced (non-metastatic and metastatic) prostate cancer since October 2005 and has looked at nearly a dozen different drugs to treat the disease.


An earlier analysis showed that the 592 men on the trial who received docetaxel lived, on average, 10 months longer than men on standard therapy. The new trial reported on the impact of docetaxel on health-related quality of life and cost-effectiveness of the addition of docetaxel and prednisolone to hormone therapy, compared to standard-of-care hormone therapy alone. Docetaxel 75 mg/m2 was administered alongside hormone therapy for six 3-weekly cycles with prednisolone 10 mg daily.


Using a standardized self-reporting tool commonly used in Europe, the researchers asked the trial participants to rate, on a five-point scale, five aspects of their health: mobility, how well they could care for themselves, their ability to perform their usual daily activities, their pain and discomfort levels, and their levels of anxiety and depression. Based on these reports, the researchers modeled changes in a man's predicted length of survival; quality-adjusted life years (QALY), a value that measures the quality and the quantity of life lived where one QALY is a year of perfect health; and incremental cost-effectiveness, which is also based on QALY as it assesses the cost-benefit of a medical treatment.


For the men with metastatic disease that had spread to organs outside of the pelvis (M1 disease), docetaxel was estimated to extend their predicted survival 0.89 years longer compared to men who received only hormone therapy, and their quality of life was preserved 0.51 years longer. For men with non-metastatic disease (M0), predicted survival was 0.78 years longer and quality of life was preserved for an additional 0.39 years with docetaxel.


"One of the key aspects we struggled with was how to truly measure quality of life," James stated. "How does one measure wanting to live a few more months to see a grandchild born even if the therapy results in difficult side effects? Although there is a concern about side effects, primarily nausea and fatigue, 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."


Adding docetaxel to standard-of-care treatment also was cost-effective for both non-metastatic and metastatic disease. QALY gains in non-metastatic patients were driven by the beneficial effect of delayed and reduced relapse, he said.


The estimated annual cost of giving docetaxel in the U.K. is about 5,000 British pounds (roughly $6,750 U.S. dollars) per QALY gained. James suggested that the potential cost-saving benefit from delaying or avoiding recurrence in the U.S. should be the same, if not greater, due to higher drug prices in the U.S.


Since STAMPEDE began, several newer drugs have come on the market, including abiraterone, an oral steroid synthesis inhibitor, which was approved by the FDA in 2011. Abiraterone has been tested in STAMPEDE, and the researchers plan to report cost-effectiveness and quality-of-life measures for this treatment later in 2018.


Docetaxel is still mandated for use by the National Health Service, but in other countries, including the U.S., the choice between using abiraterone or docetaxel is less clear. Oral abiraterone can be taken more easily than docetaxel, which is administered as a 1-hour IV infusion, but abiraterone requires a more extensive duration and intake of concomitant prednisone. A course of docetaxel costs an average patient 5,000 British pounds a year, compared to 24,000 pounds for abiraterone.


The key messages, said James, are "upfront docetaxel results in a gain in QALY in all subgroups. Our analysis suggests a high degree of certainty relating to the QALY gain associated with docetaxel. The results support the health care policy in metastatic patients and suggest the use of docetaxel in selected non-metastatic patients should be considered. At the patient level, it provides overall quality-of-life benefits. The model also predicts an eventual survival gain. At the provider level, it represents a cost-effective use of resources."


ASCO Expert Sumanta K. Pal, MD, Assistant Clinical Professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, Duarte, Calif., commented: "This study is an important step forward for men with advanced prostate cancer, and adds to existing work the novel dimension of assessing quality of life and cost-effectiveness. The fact that these results were seen in thousands of men enrolled in a long-term study boosts our faith that the findings will hold up over the long-term."


Mark L. Fuerst is a contributing writer.