Addition of Docetaxel to Androgen Deprivation Therapy for Patients with Hormone-sensitive Metastatic Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT Several randomized clinical trials (RCTs) have recently tested the early addition of docetaxel to androgen deprivation therapy (ADT) in hormone-sensitive metastatic prostate cancer (PCa). OBJECTIVE To perform a systematic review and meta-analysis of RCTs evaluating the combination of docetaxel and ADT in hormone-sensitive metastatic PCa. The primary end point was overall survival (OS). Secondary end point was progression-free survival. Exploratory subgroup analysis according to high-volume versus low-volume disease was performed. EVIDENCE ACQUISITION A systematic review of PubMed/Medline, Embase, and the proceedings of major international meetings was performed in June 2015 and updated in August 2015. Three trials were selected for inclusion. EVIDENCE SYNTHESIS Overall, 2951 patients were included in the three trials. Two trials enrolled only metastatic patients; in the third trial, 61% were metastatic. A total of 2262 patients (951 docetaxel and ADT; 1311 ADT alone) were metastatic. Most patients had a good performance status. In metastatic patients, the addition of docetaxel was associated with improved OS (hazard ratio [HR]: 0.73; 95% confidence interval [CI], 0.60-0.90; p=0.002), with nonsignificant heterogeneity among the three trials. Considering the whole study population (2951 patients), the addition of docetaxel was associated with a similar OS improvement (HR: 0.74; 95% CI, 0.61-0.91; p=0.003). Although with limited statistical power, no significant interaction was demonstrated between the addition of docetaxel and the high or low volume of disease (p=0.5). The addition of docetaxel was associated with improvement in progression-free survival (metastatic patients: HR: 0.63; 95% CI, 0.57-0.70; p<0.001). CONCLUSIONS This meta-analysis shows a significant OS benefit from concomitant administration of docetaxel and ADT in patients with metastatic hormone-sensitive PCa. PATIENT SUMMARY We synthesized the evidence available about the early administration of docetaxel in patients starting hormonal treatment for metastatic prostate cancer. Based on the results of this meta-analysis, we believe the combination of chemotherapy and hormonal treatment should be considered in fit patients.