Abiraterone Acetate, Apalutamide Likeliest to Improve Survival for Patients with Castration-Sensitive Prostate Cancer

In a comparison of systemic treatments as add-ons to androgen-deprivation therapy (ADT) for patients with metastatic castration-sensitive prostate cancer (mCSPC), abiraterone acetate (Zytiga) and apalutamide (Erleada) are likeliest to provide patients with enhanced overall survival (OS) benefit with low risks of serious adverse events.

The data, published in JAMA Oncology, also found that enzalutamide (Xtandi) would improve radiographic progression-free survival (PFS) the most, but further follow-up data is necessary to investigate the OS benefit.

“We identified 7 eligible trials constructing a scarce network in which most treatments have not been compared in head-to-head trials, which highlights the importance of the study,” wrote the investigators. “Three drugs were associated with significantly improved OS when added to ADT. Among them, abiraterone acetate was associated with significantly larger OS benefit than docetaxel, and similar OS benefit to apalutamide.”

The research team identified 7 trials investigating 6 treatment options—abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment—for 7287 total patients.

When added to ADT, treatment options that improved OS for patients with mCSPC included abiraterone acetate (HR, 0.61; 95% CI, 0.54-0.70), apalutamide (HR, 0.67; 95% CI, 0.51-0.89), and docetaxel (HR, 0.79; 95% CI, 0.71-0.89).

More, treatment options that improved radiographic PFS included enzalutamide (HR, 0.39; 95% CI, 0.30-0.50), apalutamide (HR, 0.48; 95% CI, 0.39-0.60), abiraterone acetate (HR, 0.51; 95% CI, 0.45-0.58), and docetaxel (HR, 0.67; 95% CI 0.60-0.74).

While docetaxel (odds ratio, 23.72; 95% CI, 13.37-45.15) and abiraterone acetate (odds ratio, 1.42; 95% CI, 1.10-1.83) were associated with significantly increased and slightly increased odds of serious adverse events versus placebo/no treatment, respectively, all other treatments were not associated with significant differences.

“Our results are consistent with those of a previous review that compared abiraterone acetate, docetaxel, zoledronic acid, and celecoxib [Celebrex] for mCSPC and suggested that abiraterone acetate may be the most effective treatment followed by docetaxel,” wrote the investigators. “Our findings are different from those of a review that suggested enzalutamide to be the most effective treatment; relative rankings of other drugs were similar to our estimates.”

The research team utilized bibliographic databases such as MEDLINE, Embase, and Cochrane Central, regulatory documents from the FDA and European Medicines Agency, and trial registries like ClinicalTrials.gov and the European Union clinical trials register to collect their data. The team worked to compare the effectiveness and safety of adding certain systemic treatment options to ADT.

Two limitations of the research included inconsistencies among outcome measures across each trial, which “precluded treatment comparison for many outcomes.” Because of different cutoff levels across each trial, subgroup analyses were not available.

“This study is important for patients, clinicians, and payers given the uncertainty about the optimal treatment for mCSPC, which causes significant morbidity and mortality among older men,” wrote the investigators. “The findings of this study may be applicable to patients with mCSPC in different countries because most included trials were multinational, recruiting patients from America, Europe, Asia, and Oceania.”

Reference:

Wang L, Paller CJ, Hong H, et al. Comparison of Systemic Treatments for Metastatic Castration-Sensitive Prostate Cancer. JAMA Oncology. doi:10.1001/jamaoncol.2020.6973