Should Docetaxel Be Standard of Care for Patients With Metastatic Hormone-Sensitive Prostate Cancer? Pro and Contra

K. Fizazi; C. Jenkins; I. F. Tannock


Ann Oncol. 2015;26(8):1660-1667. 

In This Article

GETUG-AFU-15 Study

The GETUG-AFU-15 study was the first to assess use of docetaxel in men with metastatic hormone-sensitive prostate cancer.[6,11] Between October 2004 and December 2008, the study enrolled 385 men with a life expectancy of at least 3 months, metastatic disease and a Karnofsky performance status ≥70%. Use of ADT was permitted for up to 2 months before study entry. Neoadjuvant and adjuvant ADT, chemotherapy or both were permitted providing these treatments were discontinued ≥12 months before study entry. Patients were randomized to receive ADT (orchiectomy or luteinizing hormone-releasing hormone agonists) alone (n = 193) or ADT plus 75 mg/m2 docetaxel every 3 weeks for nine cycles (n = 192).

The majority of patients who enrolled in the study were metastatic at diagnosis [71% (272/385)] and the remaining patients developed metastases following treatment of localized disease. A short course of prior ADT was allowed: half of the patients had received 15–60 days of ADT, while others started ADT at or within 2 weeks prior to inclusion ( Table 1 ). After a median 82.9 months follow-up, there was no statistically significant difference in the primary end point of OS between the two treatment groups: median OS was 60.9 (95% CI 46.1–71.4) months in the ADT plus docetaxel versus 46.5 (95% CI 39.1–60.6) months in the ADT-alone treatment arm (HR = 0.9; P = 0.44). At the time of final analysis, the data were reassessed in the cohort of patients with high- and low-volume disease (high-volume disease defined as visceral metastases and/or four or more bone metastases with at least one outside of the vertebral column and pelvis), but there was no significant difference in OS for either subgroup ( Table 1 ); however, this post hoc analysis was not sufficiently powered to assess a difference in OS between the subgroups. Although the study did not show any benefit in its primary end point, there was an improvement in the predefined secondary end points of both biochemical [22.9 months (95% CI 19.6–28.4) versus 12.9 (95% CI 11.9–17.7); HR = 0.72 (95% CI 0.57–0.91); P = 0.005 for ADT plus docetaxel versus ADT alone, respectively] and clinical progression-free survival (PFS) [23.5 (20.5–31.9) months versus 15.4 (12.9–19.8) months; HR = 0.75 (95% CI 0.59–0.94; P = 0.015) for ADT plus docetaxel versus ADT alone, respectively].

The median time to subsequent treatment was 20.0 months in men treated with ADT plus docetaxel compared with 15.4 months in men treated with ADT alone. Subsequent chemotherapy was mostly docetaxel (45% in the ADT plus docetaxel versus 80% in the ADT-alone treatment arms), but a few patients also received cabazitaxel (2% versus 1%). At the time of the primary analysis (2011), a total of 16 patients in the ADT plus docetaxel arm had received a novel endocrine therapy (abiraterone acetate, enzalutamide or orteronel) in a clinical study compared with 29 patients in the ADT-alone arm. Many more patients have now received these active agents, though their number is unknown.

Four potentially treatment-related deaths occurred in the ADT plus docetaxel treatment arm, two of which were neutropenia-related, and the data monitoring committee recommended use of granulocyte colony-stimulating factor (G-CSF). Subsequently, there were no further treatment-related deaths reported. A total of 72 serious adverse events were reported in the group receiving docetaxel with the most frequent being neutropenia [40 (21%)], febrile neutropenia [6 (3%)], abnormal liver function tests [3 (2%)] and neutropenia with infection [2 (1%)]. Men treated with ADT alone did not report any serious adverse events.

In summary, the GETUG-AFU-15 study showed improvement in PFS, but not in OS, the primary end point, following treatment with ADT plus docetaxel versus ADT alone.