Corticosteroid Use May Impair Enzalutamide Efficacy

Enzalutamide, an oral androgen receptor (AR) inhibitor, targets multiple steps in the AR signaling pathway.  Currently, it is FDA-approved for treating patients with metastatic castration-resistant prostate cancer who previously received docetaxel.  The approval for this indication was based on the phase 3 AFFIRM Study.2

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The AFFIRM Study, a randomized, double-blind, placebo-controlled, multinational, phase 3 study conducted in 15 countries in Africa, Australia, Europe, North America and South America, evaluated the effect of corticosteroids on patients taking enzalutamide for metastatic castration-resistant prostate cancer. All the patients in this study were randomized 2:1 to 160 mg enzalutamide once a day or placebo; 30% of patients in the enzalutamide arm and 30% of patients in placebo arm were taking corticosteroids at baseline. The patients were allowed, but not required, to take corticosteroids.  

The AFFIRM study demonstrated that enzalutamide increased median OS by 4.8 months compared to placebo.2 However, in a post-hoc multivariate model of AFFIRM data, investigators found that baseline corticosteroid use was associated with reduced overall survival, reduced time to radiographic PFS, and reduced time to PSA progression.3

Dr. Scher and his colleagues conducted a post-hoc analysis of patients in the AFFIRM study and reported Genitourinary Cancers Symposium that 48% of the patients in the enzalutamide group (n= 381) and 45% in the placebo group (n=178) had used corticosteroids.  On-study corticosteroid use was defined as oral corticosteroid use for 1 day or more while participating on the study.  Dr. Scher noted the use of corticosteroids was associated with a median OS of 11.5 months and significantly higher rates of grade 3/4 adverse events.

“We found that patients who were taking corticosteroids when they entered the study and while on the study later had worse outcomes,” said Howard Scher, MD, Chief of   Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center, New York, NY.  “The results do not exclude the fact that patients receiving corticosteroids had more advanced disease and as a group were sicker.”

He said it is noteworthy that even though patients on corticosteroids had inferior outcomes relative to those not receiving corticosteroids, the benefit of enzalutamide over placebo was apparent for both the corticosteroid and non-corticosteroid–treated patients.   Dr. Scher further emphasized that biologic properties of a tumor that is progressing on the corticosteroids may be one of the factors associated with reduced survival.