What is the role of enzalutamide (Xtandi) in the treatment of hormone-refractory prostate cancer?

Updated: Dec 29, 2020
  • Author: Martha K Terris, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Enzalutamide (Xtandi) is an oral androgen receptor inhibitor that was approved by the FDA as first-line therapy for mCRPC in September 2014. [45] The Committee for Medicinal Products for Human Use (CHMP) in Europe made a similar recommendation in October 2014. [46]  In July 2018, the FDA expanded the approval of enzalutamide to include nonmetastatic CRPC. In December 2019, enzalutamide gained FDA approval for metastatic castration-sensitive prostate cancer (mCSPC).

Approval for mCRPC was based on results from the phase III PREVAIL study, in which enzalutamide treatment significantly reduced the risk for death and radiographic progression as compared with placebo treatment. The trial was halted early after a planned interim analysis found a survival benefit in favor of enzalutamide.

In PREVAIL, enzalutamide reduced the risk for death by 29% (hazard ratio [HR], 0.71; P < 0.0001) and the risk for radiographic progression or death by 83% (HR, 0.17; P < 0.0001). Treatment with enzalutamide also delayed time to initiation of chemotherapy and time to a skeletal-related event. [47]

Enzalutamide proved superior to bicalutamide in the TERRAIN clinical trial, a double-blind, randomized phase 2 study in 375 asymptomatic or minimally symptomatic men with prostate cancer progression on ADT. Median progression-free survival was significantly longer with enzalutamide than bicalutamide (15.7 versus 5.8 months; HR, 0.44; P < 0.0001). However, 68% of patients in the enzalutamide group and 88% of those in the bicalutamide group discontinued their assigned treatment before study end, mainly due to progressive disease. [48]

The ARCHES clinical trial (n = 1150) supported the approval of enzalutamide for mCSPC. Patients were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus ADT, stratified by disease volume and prior docetaxel chemotherapy. The risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT compared with placebo plus ADT (HR, 0.39; 95% confidence interval [CI], 0.30 to 0.50; P <  0.001; median not reached vs 19.0 months). [49]


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