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

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

Disclosures

Ann Oncol. 2015;26(8):1660-1667. 

In This Article

CHAARTED Study

The more recent CHAARTED study also investigated the addition of docetaxel to ADT in metastatic hormone-sensitive disease.[5,12] Between July 2006 and November 2012, 790 men with metastatic prostate cancer who had received ≤24 months adjuvant ADT and had no signs of progression within 12 months of receiving ADT were randomized 1:1 to receive either ADT alone or ADT plus 75 mg/m2 of docetaxel every 3 weeks for six cycles within 4 months of initiating ADT.

Results were reported according to the extent of metastases: 'high-volume' disease was defined as visceral metastases and/or ≥4 bone metastases with at least one metastasis beyond the pelvis or vertebral column. Other stratification factors included: antiandrogen use beyond 30 days, age ≤70 years and >70 years, Eastern Cooperative Oncology Group (ECOG) performance status 0–1 versus 2, prior adjuvant ADT >12 months or ≤12 months and use of an FDA-approved drug for delaying skeletal-related events.

The median age was 63 years (range 36–91 years) and 98% of men had ECOG performance status 0 or 1. Most patients enrolled in the study had metastases at diagnosis (75%) and the remaining patients developed metastases following treatment of local disease ( Table 1 ). As in GETUG-AFU 15, a short course (maximum 120 days) of ADT was allowed prior to accrual: ~23% of patients had not previously received hormone therapy before study entry. The primary end point was OS and was longer in the group of patients treated with ADT plus docetaxel compared with ADT alone: median OS 57.6 versus 44.0 months, HR: 0.61 (95% CI 0.47–0.80), P = 0.0003. In a subset analysis, the greatest difference in OS occurred between the two treatment arms for the 65% of men (n = 514) with high-volume disease: median 49.2 months for those treated with ADT plus docetaxel versus 32.2 months for those treated with ADT alone (HR = 0.62, P = 0.0006). The median OS was not yet reached in the cohort of patients with low-volume disease (HR = 0.63, P = 0.14).

All of the secondary end points were met in the men who received docetaxel and ADT: PSA <0.2 ng/ml at 6 months (27.5% versus 14%, P < 0.0001) and 12 months (22.7% versus 11.7%, P < 0.0001), median time to CRPC (20.7 versus 14.7 months, P < 0.0001) and median time to clinical progression (32.7 versus 19.8 months, P < 0.0001). More than 85% of the patients (87.5%) completed all six cycles of docetaxel.

Grade 3 or 4 neutropenia, anemia, thrombocytopenia or febrile neutropenia were reported rarely in patients receiving ADT plus docetaxel, but these were likely underestimated as blood counts were not monitored routinely between cycles. Grade 3 sensory and motor neuropathy occurred in 1% of patients treated with ADT plus docetaxel. One treatment-related death was reported in the ADT plus docetaxel arm; no deaths occurred in the ADT-alone arm. After 29 months of follow-up, 137 patients receiving ADT alone and 104 patients receiving ADT plus docetaxel had died.

At disease progression, 129/174 patients (74%) who had received ADT alone and 49/145 patients (33%) who had received ADT plus docetaxel received, or resumed, treatment with docetaxel. More patients in the ADT plus docetaxel treatment arm received either abiraterone acetate or enzalutamide at disease progression [C. Sweeney (personal communication)].

In summary, the CHAARTED study suggests that combined treatment of men with ADT plus docetaxel improves not only PFS, but also OS of men with hormone-sensitive metastatic prostate cancer. Men that appear to benefit most are those with high-volume disease.

processing....