medwireNews: Abiraterone acetate or apalutamide given in combination with androgen deprivation therapy (ADT) offer the best survival outcomes for patients with metastatic castration-sensitive prostate cancer (mCSPC), a network meta-analysis shows.
“This study is important for patients, clinicians, and payers given the uncertainty about the optimal treatments for mCSPC, which causes significant morbidity and mortality among older men,” say the researchers in JAMA Oncology.
They analyzed seven randomized controlled trials involving 7287 patients with mCSPC who were given ADT with docetaxel, abiraterone acetate, enzalutamide, apalutamide, a standard nonsteroidal antiandrogen (bicalutamide, nilutamide, or flutamide), or placebo.
Abiraterone was associated with the greatest overall survival (OS) benefit, with a significant 39% reduced risk for death compared with placebo or no treatment, followed by apalutamide and docetaxel, which significantly reduced the risk for death by 33% and 21%, respectively. No significant OS benefit was seen with enzalutamide or standard nonsteroidal antiandrogens.
However, enzalutamide was associated with the greatest improvement in radiographic progression-free survival (PFS), significantly reducing the risk for radiographic progression by 61% versus placebo or no treatment. Apalutamide, abiraterone, and docetaxel also significantly reduced the risk, by 52%, 49%, and 33%, respectively, whereas standard nonsteroidal antiandrogen therapies did not.
Treatment ranking analysis reinforced these findings, showing that abiraterone had the highest probability of being the best treatment regarding OS (64%) and enzalutamide regarding radiographic PFS (88%).
“Subgroup analysis based on disease volume provided consistent results with the primary analysis,” say study author Otis Brawley (Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA) and colleagues.
With regard to safety, the incidence of serious adverse events (AEs) was “substantially increased” with docetaxel, at a significant odds ratio (OR) of 23.72 relative to placebo or no treatment, and “slightly increased” with abiraterone, at a significant OR of 1.42, report the researchers.
But treatment with apalutamide, enzalutamide, or the standard nonsteroidal antiandrogens was not associated with an increased risk for serious AEs.
These results were supported by the treatment ranking probabilities, which suggested a 100% likelihood of docetaxel being the least well tolerated and a 94% likelihood of nonsteroidal antiandrogens being the most well tolerated in terms of serious AEs.
Brawley et al therefore conclude: “This network meta-analysis suggests that abiraterone acetate and apalutamide may provide the largest and most consistent overall survival benefits with relatively low serious adverse event risks among metastatic castration-sensitive prostate cancer treatments.”
They add that “[a]lthough enzalutamide may improve [radiographic] PFS to the greatest extent, longer follow-up is needed to examine its OS benefits.”
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JAMA Oncol 2021; doi:10.1001/jamaoncol.2020.6973