NIH-funded study shows increased survival in men with metastatic prostate cancer who receive chemotherapy when starting hormone therapyMen with hormone-sensitive metastatic prostate cancer who received the chemotherapy drug docetaxel given at the start of standard hormone therapy lived more than a year longer than patients who received hormone therapy alone, according to results from a National Institutes of Health-supported randomized controlled clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago today (late breaking abstract #2).
The independent Data and Safety Monitoring Committee overseeing the trial had recommended to the National Cancer Institute (NCI), part of NIH, that the study results be made public in December 2013 because a planned interim analysis showed the prolongation in overall survival. Details from this early analysis were announced in December 2013 and the more complete data were presented at ASCO June 1, 2014.
The study enrolled 790 men with metastatic prostate cancer between July 2006 and November 2012 in a trial known as E3805. All patients started treatment by receiving a form of hormone therapy known as ADT (androgen deprivation therapy). The backbone to this therapy is suppression of testosterone. Androgens like testosterone regulate male sex characteristics and can stimulate the growth of prostate cancer cells.
Men received either ADT alone or ADT with the chemotherapy drug docetaxel every three weeks over a period of 18 weeks. In addition to examining whether the study participants lived longer with the addition of chemotherapy, investigators looked at whether the extent of a patient’s metastatic disease was high or low at the start of treatment. Approximately two thirds of patients had a high extent of metastatic disease which, according to the study, meant the cancer had spread to major organs such as the liver, or had spread to four or more bone sites, or both.
A significant improvement in overall survival was noted favoring the participants who received docetaxel chemotherapy in addition to ADT compared to those who only received ADT. Half of the patients were alive at 57.6 months with the use of early chemotherapy with ADT versus half who were alive at 44.0 months with ADT alone. Further analysis showed that patients with a high extent of metastatic disease accounted for most of the overall survival with docetaxel plus ADT (half were alive 49.2 months later with chemo-hormonal therapy versus half who were alive 32.2 months later with ADT alone). Additionally, the median time to clinical progression of the cancer was 32.7 months for men who received docetaxel plus ADT compared with 19.8 months for ADT alone. The follow-up data reported at ASCO was through mid-January of 2014.
Since docetaxel has been shown in previous clinical trials to be beneficial in men with prostate cancer that is growing despite suppressed testosterone, and is approved by the U.S. Food and Drug Administration for treatment of this later-stage disease, it is currently commercially available for use. However, because docetaxel is a chemotherapy drug associated with some toxicities, the benefit-to-risk ratio for its early use in combination with ADT is clearly in favor of offering it to patients with high-extent metastatic prostate cancer who are candidates for treatment with docetaxel, according to the trial investigators. This is the group of patients who experienced the most benefit in the current analysis. Further follow-up will be performed on patients with less extensive metastatic disease who participated in E3805 in order to define the effect of this treatment combination on these patients.
“The results of this study are practice-changing,” said lead investigator Christopher Sweeney, M.B.B.S., Dana-Farber Cancer Institute, Boston. “We have strong scientific evidence that patients with the most advanced metastatic prostate cancer benefit from the early addition of docetaxel to testosterone suppression and not waiting until the cancer has progressed with suppressed testosterone therapy. The findings of this study are important both for improving the clinical care we deliver now and in designing new clinical trials as we strive to further improve the lives of men with metastatic prostate cancer.”
E3805 was sponsored by NCI and was designed and conducted by the ECOG-ACRIN Cancer Research Group in collaboration with SWOG, Alliance for Clinical Trials in Oncology, and NRG Oncology. Sanofi, Paris, the drug manufacturer, provided the docetaxel and supported this study under a Clinical Trials Agreement with ECOG-ACRIN.
“This trial would not have been done in the United States without a large national network of investigators brought together through the NCI-supported Cooperative Group program that was capable of rapidly enrolling many patients,” said Jeff Abrams, M.D., clinical director of NCI’s Division of Cancer Treatment and Diagnosis. “Additionally, these findings are an example of how combining two approved and available treatments can produce a significant improvement in clinical outcome.
It is estimated that over 233,000 men will be diagnosed with prostate cancer in the United States in 2014 and over 29,000 men will die of the disease.
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Reference: E3805: CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer. The full protocol for this trial can be found at http://clinicaltrials.gov/ct2/show/NCT00309985. ASCO late breaking abstract #2.
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