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Sandy Srinivas, MD


Primary Survival Analysis of ENZAMET: Role of Enzalutamide in Testosterone Suppression in Prostate Cancer

By: Joshua D. Madera, MD
Posted: Tuesday, July 25, 2023

For patients with metastatic, hormone-sensitive prostate adenocarcinoma, the addition of the androgen receptor inhibitor enzalutamide to the standard-of-care therapy regimen improved overall survival, according to the primary overall survival analysis of the phase III ENZAMET trial, published in The Lancet Oncology. Therefore, this combination therapy approach should be discussed as a possible alternative treatment strategy for eligible patients, suggested Christopher J. Sweeney, MBBS, of the South Australian Immunogenomics Cancer Institute, Adelaide, and colleagues.

“We found that the addition of enzalutamide to testosterone suppression provides a consistent clinical benefit across most prognostic subgroups,” the investigators noted. “Our data also support previous work showing that patients with synchronous metastatic hormone-sensitive prostate cancer benefit from adding effective inhibition of androgen receptor signaling to testosterone suppression plus docetaxel.”

From 2014 to 2017, 1,125 patients with metastatic, hormone-sensitive prostate adenocarcinoma were recruited for the ENZAMET study. Patients were randomly assigned to receive treatment with the combination of testosterone suppression and 160 mg of enzalutamide or a standard nonsteroidal antiandrogen drug (bicalutamide, flutamide, or nilutamide). Patients were monitored until they demonstrated evidence of clinical disease progression or prohibitive toxicity.

The study findings revealed 5-year overall survival rates of 67% and 57% for patients in the enzalutamide group and standard therapy group, respectively. In addition, the median overall survival was not reached in the enzalutamide group (hazard ratio = 0.70).

Furthermore, the most commonly reported grade 3 or 4 adverse events included hypertension (10% in the enzalutamide group, 6% in the standard therapy group), febrile neutropenia associated with docetaxel use (6% vs. 6%), and fatigue (6% vs. 1%), respectively. Moreover, 13% of patients in the enzalutamide group reported grade 1 to 3 memory impairment compared with 4% of patients in the standard therapy group.

Disclosure: For full disclosures of the study authors, visit

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