July 13, 2018 – Today the U.S. Food and Drug Administration (FDA) approved enzalutamide (Xtandi) for the treatment of non-metastatic castration-resistant prostate cancer (non-metastatic CRPC). Non-metastatic CRPC is a clinical state in which PSA levels begin to rise in patients being treated with androgen deprivation therapy (ADT), but metastases are not visible yet on conventional imaging (bone or computed tomography (CT) scans). Enzalutamide was previously approved for patients with metastatic CRPC.
This new approval for enzalutamide is based on results from the randomized phase 3 PROSPER clinical trial, which was first presented publicly in February at the 2018 ASCO Genitourinary Cancers Symposium, and was published in June in the New England Journal of Medicine.
The PROSPER trial, led by PCF-funded investigator Maha Hussain, MD (Northwestern University), tested the addition of enzalutamide versus placebo to continued ADT in 1,401 men with non-metastatic CRPC who had rapidly rising PSA levels (doubling time of 10 months or less) but no evidence of disease by bone scans, CT or magnetic resonance imaging (MRI).
The addition of enzalutamide was found to delay the time to metastatic disease or death (whichever came first) by a median of 21.9 months compared with placebo (36.6 months versus 14.7 months) – representing a highly significant 71% reduction of risk for metastasis or death. Enzalutamide also significantly delayed the time before men needed additional cancer therapy, compared with placebo (median of 39.6 months vs. 17.7 months).
In February 2018, the FDA also approved apalutamide (Erleada) for non-metastatic CRPC. Prior to this year, there were no FDA-approved treatments for non-metastatic CRPC, and these patients typically continued to receive ADT alone, despite a diminishing benefit. Today, men with non-metastatic CRPC have two treatment choices, both of which significantly delay metastatic disease. It is still too early to know if the addition of either enzalutamide or apalutamide to ADT in non-metastatic CRPC improves overall survival.
PCF provided initial funding for the synthesis of both enzalutamide and apalutamide at UCLA by Drs. Michael Jung, PhD and Charles Sawyers, MD. PCF also funded early preclinical studies on both of these agents.
More information on this approval can be found here.