Survival outcomes in patients with chemotherapy-naive metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone acetate

Abstract

Objective Evaluation of the comparative effectiveness of enzalutamide and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) is limited to meta-analyses of randomized trials that exclude patients with significant comorbidities. We evaluated overall survival (OS) in patients with chemotherapy-naive mCRPC treated with enzalutamide or abiraterone acetate (abiraterone) in a real-world single payer setting. Methods A retrospective analysis (4/1/2014–3/31/2018) of the Veterans Health Administration (VHA) database was conducted. Patients with mCRPC had ≥1 pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following disease progression on surgical/medical castration, without chemotherapy <12 months prior to index date. Patients had continuous VHA enrollment for ≥12 months pre-index date and were followed until death, disenrollment, or end of study. Kaplan–Meier analysis and multivariable Cox proportional hazards regression models examined the OS treatment effect. Results Patients with chemotherapy-naive mCRPC (N = 3174; enzalutamide, n = 1229; abiraterone, n = 1945) had mean ages of 74 and 73 years, respectively. Median follow-up was 18.27 and 19.07 months with enzalutamide and abiraterone, respectively. Enzalutamide-treated patients had longer median treatment duration than abiraterone-treated patients (9.93 vs 8.47 months, respectively, p = 0.0008). After baseline comorbidity adjustment, enzalutamide-treated patients had a 16% reduced risk of death (hazard ratio [HR] = 0.84; 95% CI, 0.76–0.94; p = 0.0012). For patients who remained on first line-therapy only, enzalutamide-treated patients had improved OS versus abiraterone-treated patients (HR = 0.71; 95% CI, 0.62–0.82). Enzalutamide-treated patients who crossed over to abiraterone had a comparable risk of death versus abiraterone-treated patients who crossed over to enzalutamide (HR = 0.91; 95% CI, 0.74–1.13). These results were confirmed by sensitivity analysis, which considered prognostic variables. Conclusions Retrospective analysis of the VHA database indicated that chemotherapy-naive patients with mCRPC initiating therapy with enzalutamide had improved survival versus abiraterone.

RNA Biomarkers as a Response Measure for Survival in Patients with Metastatic Castration-Resistant Prostate Cancer

“…The median OS rates found in our study are slightly shorter compared to the reported OS rates from the registration studies of enzalutamide and abiraterone acetate (26.8 vs. 35.5 months and 28.4 vs. 34.7 months respectively) [ 35 , 36 ]. Though, our median survival rates are in line with a large previously published real-life cohort of chemotherapy-naïve patients treated with enzalutamide or abiraterone acetate (median OS 29.6 and 25.9 months respectively) [ 37 ]. Our cohort is therefore considered representative for a real-life first line treated cohort of patients with mCRPC.…”

Enzalutamide Versus Abiraterone plus Prednisolone Before Chemotherapy for Castration-resistant Prostate Cancer: A Multicenter Randomized Controlled Trial

“…Interestingly, a recent systematic review and meta-analysis revealed no significant difference in OS improvement between ENZ and ABI, but ENZ was superior to ABI in improving rPFS and TTPP for patients with metastatic CRPC [25] . In addition, a large retrospective analysis of the Veterans Health Administration database revealed that patients treated with ENZ had a 16% lower risk of death in comparison to those treated with ABI (HR 0.84, 95% CI 0.76–0.94; p = 0.0012) [26] . These data indicate a stronger ability of ENZ to inhibit androgen receptor signaling as a single agent.…”

Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer

“…It must be noted, however, that abiraterone trials (COU-AA-301, COU-AA-302) used prednisone (an agent with known antitumor activity in mCRPC) as a control arm, whereas enzalutamide trials (AFFIRM, PREVAIL) used placebo as a control arm. Results from a recent retrospective study of 3174 patients with chemotherapy-naive mCRPC treated with first-line enzalutamide or abiraterone acetate, those who received enzalutamide had significantly better OS compared to those who were treated with abiraterone (HR 0.84, 95% CI 0.76-0.94) [45]. The different toxicity profile of abiraterone and enzalutamide may assist during the treatment selection in some men with mCRPC, although they are both generally well tolerated and safe in the vast majority of patients.…”