Addition of Docetaxel to Androgen Receptor Axis-targeted Therapy and Androgen Deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis

CONTEXT: Randomized controlled trials (RCTs) have shown that addition of docetaxel or androgen receptor axis-targeted therapy (ARAT) to androgen deprivation therapy (ADT) or addition of ARAT to ADT and docetaxel improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). However, it is unknown whether docetaxel, when given as part of triplet therapy, has an independent OS benefit. OBJECTIVE: To compare the efficacy of ADT plus ARAT with the triplet of ADT, ARAT, and docetaxel through a network meta-analysis (NMA) of RCTs in mHSPC. EVIDENCE ACQUISITION: Bibliographic databases and conference proceedings were searched in March 2022 for RCTs that evaluated the addition of docetaxel, ARAT, or both to ADT in mHSPC. The primary endpoint was OS. Standard random-effect NMA and Bayesian analyses were performed to compare ADT plus ARAT with triplet therapy. EVIDENCE SYNTHESIS: Eleven RCTs (n = 11 546) were eligible. Compared with ADT plus ARAT, the triplet had a nonsignificant OS benefit (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.68-1.16), while ADT plus docetaxel (HR 1.16 [0.94-1.43]) and ADT alone (HR 1.46 [1.30-1.64]) had an increased risk of death. By P-score ordering, the triplet was the most effective treatment strategy (P score = 0.936) followed by ADT plus ARAT (P score = 0.704). The triplet had a 77% likelihood of being the best treatment strategy compared with a 23% likelihood for ADT plus ARAT. CONCLUSIONS: The triplet of ADT, ARAT, and docetaxel was the highest ranked treatment strategy, but it did not confer a statistically significant OS benefit over ADT plus ARAT. This NMA provides the highest-level comparative evidence for these treatment approaches in the initial management of mHSPC. PATIENT SUMMARY: We synthesized the available evidence from clinical trials conducted in newly diagnosed metastatic prostate cancer to compare the survival of patients receiving triplet therapy (androgen receptor axis-targeted therapy [ARAT], androgen deprivation therapy [ADT], and docetaxel) with those receiving only ARAT and ADT. We conclude that the triplet is a somewhat more effective treatment approach.