Docetaxel With ADT Improves Survival for Metastatic Prostate Cancer Patients

Christopher Sweeney, MBBS; photo by © ASCO/Silas Crews 2014

Results from the phase III E3805 clinical trial show that adding docetaxel to standard hormone therapy extends survival for men with metastatic hormone-sensitive prostate cancer by 13.6 months. The extension of survival was greatest among men with extensive disease-a difference of 17 months. The trial was led by the Eastern Cooperative Oncology Group and funded by the National Cancer Institute. The results (abstract LBA2) were presented at the plenary session by Christopher Sweeney, MBBS, a medical oncologist at Dana-Farber Cancer Institute in Boston, at a press briefing at the American Society of Clinical Oncology Annual Meeting, held May 30–June 3 in Chicago.

“I am not aware of any prostate cancer study that has offered this magnitude of improvement in survival,” said current ASCO president Clifford Hudis, MD, chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center in New York City, at the press briefing. “Across all the solid tumors, this is an almost unprecedented improvement in median survival.”

What is particularly notable is that docetaxel is a relatively inexpensive agent compared with newer targeted therapies that are used to treat advanced prostate cancer.

“Six cycles of docetaxel in addition to ADT [androgen deprivation therapy] represents an appropriate option for men with metastatic prostate cancer commencing ADT who are suitable for docetaxel therapy,” said Sweeney. “This is the first study to identify a strategy that prolongs survival in newly diagnosed metastatic prostate cancer. The benefit in patients with a high volume of metastatic disease is clear and justifies the treatment burden.”

Still, Sweeney noted that longer follow-up is required for patients with low-volume metastatic disease to assess the benefit of the regimen.

ADT is currently the standard first-line therapy for men with hormone-sensitive prostate cancer. For those men who become ADT-resistant, chemotherapy is the next course of treatment. Still, despite these therapies, approximately 30,000 men in the United States progress and die of hormone-resistant prostate cancer every year.

The researchers tested the hypothesis that earlier use of docetaxel-an active agent for castration-resistant prostate cancer (CRPC)-would lead to more cancer killing when the tumors are more sensitive to therapy in general, resulting in increased longevity, Sweeney told Cancer Network.

Seven-hundred and ninety men with newly diagnosed metastatic prostate cancer were randomized one-to-one to receive either ADT or ADT combined with docetaxel for 18 weeks. Docetaxel was given at 75 mg/m² every 3 weeks for 6 cycles. Patients were stratified by volume of disease, age, and prior adjuvant therapy. The median age of patients was 63 years.

At a median follow-up of 29 months, median overall survival (OS) was 57.6 months in the combination therapy group compared with 44 months in the ADT alone group (hazard ratio [HR] = 0.61; P < .0003). In the combination group, 101 deaths occurred compared with 136 deaths in the control group.

Among the 520 patients with extensive disease (66% of the patients in the trial), including bone metastases, those in the combination group had a median OS of 49.2 months compared with 32.2 months in the ADT alone group (HR = 0.62; P = .0012).

The median time to clinical progression was 19.8 months in the ADT alone group compared with 32.7 months in the combination therapy group (HR = 0.49; P < .0001).

High-grade toxicities among patients in the combination group included neutropenic fever (4% grade 3, 2% grade 4), 1% grade 3 sensory neuropathy, and 1% grade 3 motor neuropathy. One death due to treatment occurred in this group as well.

Patients with low-volume disease are still being followed to evaluate survival. Quality of life is also currently being evaluated.

According to Sweeney, the reason why men with more extensive disease benefited more in this initial analysis is that they are more likely to die of the disease and the regimen resulted in greater cancer control and lower frequency of cancer deaths, while for those men with low-volume disease, ADT alone may be able to control their cancer for 5 or more years. Patients with low-volume disease are more likely to live longer in general and die of non–prostate cancer causes, thus diluting the effect of the therapy.

“For example it may be more beneficial in a 55-year-old with low volume than a 78-year-old with low volume, as the older patient may die of heart disease in the meantime. [If this is the case], we may need to take competing risks of death into account,” said Sweeney.