Abiraterone, Docetaxel Best With ADT for Metastatic Prostate Cancer

A meta-analysis suggests that abiraterone acetate plus prednisolone/prednisone (AAP) may be the most effective therapy added to androgen deprivation therapy (ADT) for men with metastatic hormone-naive prostate cancer (mHNPC). The results also supported the use of docetaxel along with ADT.

Prior analyses from the STOPCAP collaboration showed improved survival when AAP or docetaxel, but not zoledronic acid (ZA), were added to ADT, while other trial evidence also supported adding celecoxib and ZA to ADT. “Network meta-analysis, which takes advantage of both direct and indirect comparisons, is…needed to determine reliably which is the optimal treatment(s), and so to inform patients, clinicians, and policymakers,” wrote study authors led by Claire Vale, PhD, of the MRC Clinical Trials Unit in London.

The new analysis was based on the results of 6 completed trials that included 6,204 men with mHNPC. Two of these compared ADT with ADT plus ZA; two compared ADT with ADT plus docetaxel; one compared ADT with ADT plus AAP; and the final trial, the STAMPEDE study, included six separate comparisons of the various treatments. The results of the analysis were published in Annals of Oncology.

The primary analysis was of overall survival. Compared with ADT alone, AAP along with ADT had a hazard ratio (HR) of 0.61 (95% CI, 0.53–0.71). Docetaxel along with ADT also showed improved overall survival, with an HR of 0.77 (95% CI, 0.68–0.87), as did ZA plus docetaxel along with ADT, with an HR of 0.79 (95% CI, 0.66–0.94) and ZA plus celecoxib along with ADT, with an HR of 0.78 (95% CI, 0.62–0.97).

ZA combined with ADT did not yield a significant advantage, with an HR of 0.90 (95% CI, 0.79–1.03); the same was true for celecoxib combined with ADT, with an HR of 0.94 (95% CI, 0.75–1.17).

An analysis that ranked the various treatments found that AAP combined with ADT has the highest probability of being the most effective therapy, at 94.2%. This was followed by docetaxel, at 34.9%, and then ZA plus docetaxel, at 30.3%. The highest probability of being the worst treatment was seen with ADT alone, at 67.2%, followed by celecoxib in combination with ADT, at 27.0%.

Failure-free survival results were similar, with a significant advantage over ADT alone seen with AAP, docetaxel, and ZA plus docetaxel. AAP plus ADT was again the most likely to be the most effective treatment (100%), and ADT alone was most likely to be the worst treatment (73%).

“Based on the current data, either AAP or docetaxel alongside ADT improves the survival of men with mHNPC,” the authors concluded, noting that uncertainty remains regarding the difference in absolute magnitude of benefit between the treatments. “Our results support the use of either AAP or docetaxel alongside ADT in men with mHNPC. …To fully account for patient variability across trials, changes in prognosis or treatment effects over time, and the potential impact of treatment on progression, a network meta-analysis based on individual participant data is currently in development.”