Comparison of Systemic Treatments for Metastatic Castration-Sensitive Prostate Cancer

Abstract

IMPORTANCE Multiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely varied costs.OBJECTIVE To compare the effectiveness and safety determined in randomized clinical trials of systemic treatments for mCSPC. DATA SOURCES Bibliographic databases (MEDLINE, Embase, and Cochrane Central), regulatory documents (US Food and Drug Administration and European Medicines Agency), and trial registries (ClinicalTrials.gov and European Union clinical trials register) were searched from inception through November 5, 2019.STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS Eligible studies were randomized clinical trials evaluating the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for treatment of mCSPC. Two investigators independently performed screening. Discrepancies were resolved through consensus. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by bayesian network meta-analysis and survival models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. MAIN OUTCOMES AND MEASURESOverall survival, radiographic progression-free survival, and serious adverse events (SAEs).RESULTS Seven trials with 7287 patients comparing 6 treatments (abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment) were identified. Ordered from the most to the least effective determined by results of clinical trials, treatments associated with improved overall survival when added to ADT included abiraterone acetate (hazard ratio [HR], 0.61; 95% credible interval [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); treatments associated with improved radiographic progression-free survival when added to ADT 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). Docetaxel was associated with substantially increased SAEs (odds ratio, 23.72; 95% CI,), abiraterone acetate with slightly increased SAEs (odds ratio, 1.42; 95% CI, 1.10-1.83), and other treatments with no significant increase in SAEs. Risk of bias was noted for 4 trials with open-label design, 3 trials with missing data, and 2 trials with potential unprespecified analyses. CONCLUSIONS AND RELEVANCEIn this network meta-analysis, as add-on treatments to ADT, abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks. Although enzalutamide may improve radiographic progression-free survival to the greatest extent, longer follow-up is needed to examine the overall survival benefits associated with enzalutamide.

Useful predictors of progression‐free survival for Japanese patients with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer who received upfront abiraterone acetate

“…Regarding the treatment of mCSPC patients, according to the network meta‐analysis, ADT plus Abi or Apa might provide the largest OS benefits, with relatively low serious AE risks. Enz might improve radiographic PFS to the greatest extent, but a longer follow up is required to examine the OS benefits associated with Enz 18 . Recently, Harada et al .…”

Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high‐risk metastatic hormone‐sensitive prostate cancer

“…Four published network meta-analysis studies have aimed to clarify this issue, of which two showed the utility of enzalutamide in OS 20,21 and the others demonstrated significant survival benefits of abiraterone in all patients. 22,23 Thus, the issue of which agent constitutes the best treatment choice is thus still controversial.…”

Characteristics and progression‐free survival of Afro‐Caribbean men with metastatic hormone‐sensitive prostate cancer at the time of diagnosis

“…For many years, first‐generation hormone therapy was the gold standard treatment for metastatic forms of prostate cancer. Since 2015, the advent of recent therapies, such as chemotherapy with docetaxel and second‐generation hormone therapies (abiraterone, enzalutamide, apalutamide) have enriched the management options for metastatic prostate cancer, with an improvement in overall and progression‐free survival (PFS) 7–12 …”