Enzalutamide in European and North American men participating in the AFFIRM trial

Abstract

ObjectiveTo explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311).Patients and MethodsPhase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis.ResultsEnzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry.ConclusionThis post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions.

Enzalutamide: targeting the androgen signalling pathway in metastatic castration‐resistant prostate cancer

“…healthrelated quality of life, time to first skeletal-related event and pain) [50,52]. Additional secondary analyses have shown consistent benefits in OS, rPFS and time to PSA progression with enzalutamide in elderly (≥75 years) and younger (<75 years) patients [53], in patients with different levels of disease severity assessed by baseline PSA levels, and in both North American-and European-treated patients [54,55].…”

Development of enzalutamide for metastatic castration‐resistant prostate cancer

“…Benefit was observed in patients <75 and ࣙ75 years of age, 85 in those with or without visceral liver and lung metastases, and in North American and European patients. 12,86,87 Enzalutamide consistently improved OS, rPFS, and time to PSA progression compared with placebo, regardless of baseline PSA levels. 88 While baseline corticosteroid use was associated with reduced OS, enzalutamide was consistently superior to placebo regardless of baseline corticosteroid use in the AFFIRM trial.…”

“…Sipuleucel‐T is a cellular immunotherapy that has been shown to increase overall survival (OS) in patients with asymptomatic or minimally symptomatic CRPC . Radioisotopic radium‐223 is approved for use in patients with symptomatic CRPC both pre‐ and post‐docetaxel to treat bone metastases, a major cause of death, disability, and decrease in quality of life…”

“…9 Sipuleucel-T is a cellular immunotherapy that has been shown to increase overall survival (OS) in patients with asymptomatic or minimally symptomatic CRPC. 10,11 Radioisotopic radium-223 is approved for use in patients with symptomatic CRPC both pre-and post-docetaxel to treat bone metastases, 12 a major cause of death, disability, and decrease in quality of life. 13 Because disease progression is almost always accompanied by an increase in PSA, and PSA gene expression is activated by the androgen receptor (AR), researchers have aggressively explored mechanisms by which progressive disease may be driven by AR signaling.…”

Drug design strategies for the treatment of prostate cancer

“…In the PREVAIL study, enzalutamide was evaluated in men who had progressed on androgen-deprivation therapy but who had not undergone chemotherapy. Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with prostate cancer [44]. The AFFIRM trial is a Phase III placebocontrolled trial that showed an improved OS with enzalutamide compared to placebo, 18.4 versus 13.6 months, respectively [45].…”