Drug combo offers survival benefit in advanced prostate cancer

Men with hormone-sensitive metastatic prostate cancer who received docetaxel (Taxotere) given at the start of standard hormone therapy lived longer than patients who received hormone therapy alone, according to early study results that the lead investigator called “practice changing.”

The randomized controlled clinical trial was supported by the National Institutes of Health.

The independent Data and Safety Monitoring Committee overseeing the trial recommended to the National Cancer Institute that the study results be made public because a recent planned interim analysis showed the prolongation in overall survival. Full details from this early analysis will be presented at a scientific meeting in 2014 and in a peer-reviewed publication, the NIH said in a news release.

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 androgen deprivation therapy (ADT).

Men received either ADT alone or ADT with docetaxel every 3 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. In approximately two-thirds of patients, the disease had spread to major organs such as the liver, had a spread resulting in four or more bone lesions, or both.

A significant improvement in the overall survival was noted favoring the participants who had received docetaxel chemotherapy in addition to the ADT compared to ADT alone (3-year survival rates of 69% vs. 52.5%, respectively). Further analysis showed that patients with a high extent of metastatic disease accounted for most of the benefit in the overall survival from docetaxel plus ADT (3-year survival rates of 63.4% vs. 43.9% for ADT alone). Median follow-up to date is 2 years.

The NIH noted that since docetaxel has been shown in previous clinical trials to be beneficial in ADT-resistant disease and is approved by the FDA for treatment of late-stage prostate cancer, it is available for use now. However, because it is a chemotherapy drug associated with some toxicities, its use in combination with ADT at this time should be restricted 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, MD, of 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 ADT and not waiting until the cancer has progressed on hormonal 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.

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