ENZAMET Trial OS Analysis: Testosterone Suppression Plus Enzalutamide or Antiandrogen Therapy

By Emily Menendez - Last Updated: April 14, 2023

The open-label, randomized, phase 3 ENZAMET trial began in 2014 and studied the effect of testosterone suppression in combination with either enzalutamide or nonsteroidal antiandrogen therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

New research has reported updates on the primary overall survival (OS) analysis to define the benefit of enzalutamide treatment in various prognostic subgroups, including synchronous and metachronous high-volume or low-volume disease and in patients who received concurrent docetaxel.

The ENZAMET trial was a worldwide study carried out in Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States. It was conducted at 83 medical sites, including clinics, hospitals, and university centers. A total of 1125 patients with mHSPC aged 18 years or older were enrolled in the study between March 2014 and March 2017 and randomly assigned 1:1 to receive either testosterone suppression plus oral enzalutamide (160 mg once per day) or a nonsteroidal antiandrogen (control group) until clinical disease progression or prohibitive toxicity occurred.

Concurrent intravenous docetaxel (75 mg/m2) was allowed for up to 6 cycles once every 3 weeks, and testosterone suppression was allowed for up to 12 weeks before randomization and for up to 24 months as adjuvant therapy. The primary end point was OS in the intention-to-treat population.

An updated survival status based on an analysis of the trial conducted in January 2022 reported a total of 476 (42%) deaths. After a median follow-up of 68 months, the median OS was not reached. The 5-year OS rates of the control group and the enzalutamide group were 57% and 67%, respectively. OS benefits with enzalutamide were consistent across predefined prognostic subgroups and planned use of concurrent docetaxel. The most common grade 3-4 adverse events were febrile neutropenia associated with docetaxel use, fatigue, and hypertension.

Adding enzalutamide to standard-of-care treatment provided sustained improvement in OS for patients with mHSPC and should be considered a viable treatment option for eligible patients.