Apalutamide Receives FDA Approval for Metastatic Hormone-Sensitive Prostate Cancer

For metastatic castration-sensitive prostate cancer (sensitive to male hormone suppression), apalutamide (Erleada) received approval on 17 September 2019 from the US Food and Drug Administration (FDA). Apalutamide had received, in 2018 for nonmetastatic castration-resistant prostate cancer, its first approval in that setting.

FDA approval for this population came from a randomized, double-blind, placebo-controlled, multicenter trial enrolling 1052 patients with metastatic castration-sensitive prostate cancer, TITAN , and its results.

What Is Apalutamide?

Its US brand name is Erleada, and its active ingredient is apalutamide . The drug was discovered in 2010. It prevents androgens such as testosterone and dihydrotestosterone from binding to androgen receptorsabundant in prostate cells, thereby blocking these male hormones’ effects on the prostate and other tissues.

Global Cancer Statisticsshow that in 2018, 1 million 280 thousand men were diagnosed with prostate cancer. Approximately 10% present with metastatic (advanced, stage 4) disease. This indicates the new approval concerns more than 100 thousand patients globally.

Details of the TITAN Study in Metastatic Prostate Cancer

Patients received oral apalutamide 240 mg or placebo . All patients received androgen deprivation therapy with a concomitant gonadotropin-releasing hormone analogue or prior bilateral orchiectomy (testicular removal to reduce testosterone, now less preferred). Both high- and low-volume disease were included.

• TITAN showed statistically significant improvements in overall survival and radiographic progression-free survival with apalutamide.
• At a prespecified interim analysis, apalutamide reduced mortality risk by 33% (overall survival hazard ratio 0,67).
• Median overall survival had not been reached in either arm.
• Apalutamide reduced progression risk by 52% (hazard ratio 0,48).
• Median progression-free survival was not reached with apalutamide plus androgen deprivation because more than half had no progression; with placebo plus androgen deprivation it was 22.1 months.

The most common side effects with apalutamide (frequency ≥10%) were fatigue, arthralgia (joint pain), rash, reduced appetite, falls, weight loss, hypertension, hot flushes, diarrhea and fractures.

The recommended apalutamide doseis 240 mg orally once daily with or without food (four 60 mg tablets). Patients should also receive a gonadotropin-releasing hormone (GnRH) analogue or have undergone bilateral orchiectomy.