Enzalutamide Approved for Non-Metastatic Castration Sensitive Prostate Cancer With Biochemical Recurrence

The US Food and Drug Administration (FDA) has approved enzalutamide for the treatment of patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis.

This regulatory decision was based on efficacy results from the EMBARK trial. In this randomized, controlled, phase 3 trial, 1068 patients with non-metastatic castration sensitive prostate cancer with biochemical recurrence at high risk for metastasis were enrolled. All patients had undergone either definitive radical prostatectomy or definitive radiotherapy with curative intent, had PSA doubling time ≤ 9 months, and were not eligible for salvage radiotherapy.

Patients were randomized on a 1-to-1-to-1 basis to receive blinded 160 mg enzalutamide once daily plus leuprolide, open-label single-agent 160 mg enzalutamide once daily, or blinded placebo once daily plus leuprolide. The major efficacy outcome measure was metastasis-free survival (MFS), as assessed by blinded independent central review, for enzalutamide plus leuprolide compared with placebo plus leuprolide. Additional outcome measures included MFS for enzalutamide monotherapy compared to placebo plus leuprolide and overall survival.

There was a statistically significant improvement in MFS for enzalutamide plus leuprolide compared to placebo plus leuprolide; the median MFS was not reached in either arm (hazard ratio [HR] 0.42; 95% confidence interval [CI], 0.30 to 0.61; P < .0001). There was also a statistically significant improvement in MFS for enzalutamide monotherapy compared to placebo plus leuprolide (HR, 0.63; 95% CI, 0.46 to 0.87; P = .0049). At the time of analysis, overall survival data had not yet matured.

The most common adverse events, occurring at ≥20% incidence among patients who received enzalutamide plus leuprolide, were hot flush, musculoskeletal pain, fatigue, fall, and hemorrhage. Among patients who received enzalutamide monotherapy, the most common adverse events were fatigue, gynecomastia, musculoskeletal pain, breast tenderness, hot flush, and hemorrhage.

The recommended dose for enzalutamide is 160 mg orally, once daily with or without food until disease progression or unacceptable toxicity. Enzalutamide may be administered with or without gonadotropin hormone-releasing hormone (GnRH) analog. Enzalutamide treatment may be suspended if PSA is undetectable after 36 weeks of therapy and reinitiated when PSA has increased to ≥ 2.0 ng/mL for patients with prior radical prostatectomy or ≥5.0 ng/mL for patients with prior primary radiation therapy.

Source:

FDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence. US Food and Drug Administration. Published November 17, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-enzalutamide-non-metastatic-castration-sensitive-prostate-cancer-biochemical-recurrence