medwireNews: Adding docetaxel, abiraterone acetate, enzalutamide, or apalutamide to androgen deprivation therapy (ADT) significantly improves survival for men with metastatic hormone-sensitive prostate cancer (mHSPC), with little difference between each drug, a network meta-analysis shows.
Declan Murphy (Peter MacCallum Cancer Centre, Parkville, Victoria, Australia) and colleagues say that their results do not “provide a clear answer regarding which agent might be preferred, [but] suggest that enzalutamide in combination with ADT may be the most effective in terms of delaying death from any cause.”
They add: “This is an important development from previous [network meta-analyses] that did not include studies on apalutamide and enzalutamide, and concluded that abiraterone acetate was likely the preferred treatment option.”
The analysis included seven randomized clinical trials among patients receiving first-line therapy for mHSPC with a combination of ADT plus taxane-based chemotherapy or androgen receptor-targeted therapy. Docetaxel was the additional agent used in three trials, abiraterone plus prednisone was used in two trials, as was enzalutamide, while one trial examined apalutamide in combination with ADT.
The researchers report in European Urology that all four combinations significantly improved overall (OS) compared with ADT alone, with hazard ratios (HRs) of 0.81, 0.69, 0.64, and 0.53 for docetaxel, abiraterone, apalutamide, and enzalutamide, respectively.
There were no significant differences in OS between any of the combinations but, using rank probabilities, Murphy and team calculated that enzalutamide plus ADT was the most likely to be ranked as the number 1 treatment for prolonging OS, with an estimated probability of 76.9% versus just 19.8% for apalutamide.
The team also carried out subgroup analyses based on the volume of disease and found that for low-volume disease defined according to CHAARTED criteria, only enzalutamide plus ADT significantly improved OS relative to ADT alone (HR=0.38). For high-volume disease, all four combinations were superior to ADT, with HRs ranging from 0.62 with enzalutamide to 0.72 with docetaxel.
Murphy and co-authors conclude that “[s]ubtle differences between these options allow clinicians considerable flexibility when selecting options for individual patients.”
They add: “We await the results of ongoing randomised studies directly comparing upfront combination interventions to provide further guidance for clinicians.
“In the meantime, it is reasonable to conclude that upfront combination approaches are the new standard of care for men with mHSPC, and ADT alone will likely only be used in limited circumstances or when economic factors constrain options.”
By Laura Cowen
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