"Among systemic mCSPC treatments currently approved by the U.S. Food and Drug Administration and recommended by clinical guidelines, abiraterone acetate was associated with the most considerable overall survival benefit with relatively low risks of serious adverse events," Dr. Lin Wang of Johns Hopkins University Bloomberg School of Public Health, in Baltimore, Maryland, told Reuters Health by email.
In a paper in JAMA Oncology, Dr. Wang and colleagues note that mCSPC is associated with high mortality, with a five-year survival rate of only 30%.
A number of treatments added to ADT can delay disease progression. However, the authors say that the lack of head-to-head trials of the effectiveness and safety of the agents involved means there is little information available to guide an optimal choice.
Costs also vary dramatically, For example, a planned course of docetaxel is estimated to cost $627 compared to more than $231,000 for apalutamide.
To help provide more information, after excluding cluster and dose-escalation studies, the researchers conducted a network meta-analysis using data from seven randomized trials involving more than 7,200 patients.
In addition to ADT, patients received docetaxel, abiraterone acetate, palutamide or enzalutamide. Outcomes was compared with any active drug, placebo, or no additional treatment.
Median follow-up was for at least 12 months. The drugs yielding significantly improved overall survival were abiraterone acetate (hazard ratio, 0.61), apalutamide (HR, 0.67) and docetaxel (HR, 0.79).
The drugs associated with significantly improved radiographic progression-free survival were enzalutamide (HR, 0.39), apalutamide (HR, 0.48), abiraterone acetate (HR, 0.51) and docetaxel (HR, 0.67).
However, docetaxel was associated with "substantially increased" serious adverse events (odds ratio, 23.72), whereas abiraterone acetate presented a slightly raised risk (OR, 1.42). There was no significantly increased risk with the other agents.
The researchers conclude that "abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks."
They go on to point out that although "enzalutamide may improve radiographic progression-free survival to the greatest extent longer follow-up is needed to examine the overall survival benefits."
Dr. Daniel Spratt, chief of the genitourinary radiotherapy program at Michigan Medicine, in Ann Arbor, told Reuters Health by email that the benefit of the authors' approach "is that randomized trials will not be done in all of the comparisons tested given the numerous agents now approved and available. The limitation of their analysis is that the patients enrolled are not the same in numerous ways, and can't be harmonized without individual patient data."
"Despite this," said Dr. Spratt, "they demonstrate that there were almost no statistically significant differences in overall survival between any of the newer systemic therapies. Furthermore, the results and Bayesian ranks demonstrated that none of these newer systemic therapies had a greater than 75% probability of being superior. This provides reassurance that all of these agents have a role in the treatment of mCRPC over ADT alone."
The study was supported by the Dyar Memorial Fund and Pharmaceutical Research and Manufacturers of America Foundation 2020 Predoctoral Fellowship in Health Outcomes Research.
SOURCE: https://bit.ly/38Unotr JAMA Oncology, online January 14, 2021.
By David Douglas
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