Docetaxel plus Androgen Deprivation Therapy for Metastatic Prostate Cancer

Chicago—Patients with hormone-sensitive newly metastatic prostate cancer who received docetaxel with androgen deprivation therapy (ADT) had a significant improvement in overall survival compared with a group that received ADT alone, according to a randomized, phase 3 trial.

The median overall survival was 57.6 months in the docetaxel plus ADT group and 44 months in the ADT alone group (hazard ratio [HR], 0.61; P=.0003). There was a survival benefit in all subgroups that the authors analyzed.

In patients with high volume disease, the median overall survival was 49.2 months and 32.2 months, respectively (HR, 0.6; P=.0006). In patients with low volume disease, the median overall survival had not been reached at a median follow-up of 29 months.

Christopher Sweeney, MBBS, the study’s lead author, presented the results during a plenary session at ASCO meeting. The study was funded by the National Cancer Institute and led by the Eastern Cooperative Oncology Group (ECOG) in conjunction with the Southwest Oncology Group. Sanofi provided the researchers with docetaxel for use during the study.

Dr. Sweeney said that researchers in 1941 found that testosterone suppression resulted in prostate cancer regression, leading to ADT becoming the standard of care for patients with hormone-sensitive newly metastatic prostate cancer. Although reports have indicated stage migration since the introduction of the prostate-specific antigen test has led to longer overall survival, he added that patients’ survival after ADT varied from a few months to several years. Patients with visceral metastases and a higher number of bone metastases and/or disease beyond the axial skeleton have shorter responses, according to Dr. Sweeney. Docetaxal was the first agent to increase overall survival for metastatic, castration-resistant prostate cancer

The CHAARTED [Chemohormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer] study was designed to evaluate if adding early chemotherapy would be beneficial and prolong survival. Patients were eligible if they had metastatic prostate cancer, prior ADT limited to 120 days before randomization, as well as adjuvant therapy <24 months, and an ECOG performance status score of 0, 1, or 2. They were also required to have not taken docetaxel previously and have liver, bone marrow, renal, cardiac, pulmonary, and neurological function suitable for docetaxel.

Patients were randomized to receive ADT plus 75 mg/m² of docetaxel every 21 days for a maximum of 6 cycles or ADT alone. The researchers did not allow intermittent ADT. They required standard dexamethasone premedication, although daily prednisone was optional.

Between July 28, 2006, and November 21, 2012, the authors enrolled 790 men in the study. The data presented at the ASCO meeting included information through January 16, 2014.

At a median follow-up of 29 months, 136 deaths had occurred in the ADT alone group and 101 deaths had occurred in the ADT plus docetaxel group. In each group, 83% of the deaths were due to prostate cancer. Only 1 death (in the docetaxel plus ADT group) was due to the study treatment.

At baseline, the groups were well-balanced. The median age was 64 years, 88% of patients were white, 70% had an ECOG status score of 0, 20% had an ECOG status score of 1, and 10% had an ECOG status score of 2.