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

Abstract

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.

Keywords: Androgen deprivation therapy; Chemotherapy; Docetaxel; Hormone-sensitive prostate cancer; Meta-analysis; Systematic review.