December 16, 2019 – Today the U.S. Food and Drug Administration (FDA) approved a new use for enzalutamide (Xtandi®) for the treatment of metastatic hormone-sensitive (aka, “castration-sensitive”) prostate cancer (mHSPC). Enzalutamide has previously been FDA-approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC).
PCF funded the initial synthesis of enzalutamide at UCLA by chemist Michael Jung, PhD, in collaboration with prostate cancer physician-scientist Charles Sawyers, MD (now at Memorial Sloan Kettering Cancer Center).
mHSPC refers to men whose prostate cancer has spread to areas of the body outside of the prostate itself, and who are responsive to testosterone-lowering agents. This may refer to men who have had prior surgery or radiation and recurred, or men who were initially diagnosed with disease that was already metastatic (outside the prostate). Patients who are “hormone-sensitive” may have previously received androgen deprivation therapy (ADT) for a certain amount of time, but their cancer has not yet developed resistance to ADT.
This approval is based on results from the randomized phase 3 ARCHES clinical trial, which was presented at the 2019 Genitourinary Cancers Symposium held in February, and published in the prestigious medical journal, the Journal of Clinical Oncology.
The ARCHES trial, led by PCF-funded investigator Dr. Andrew Armstrong, of Duke Cancer Institute, tested the addition of enzalutamide vs. placebo to ADT in 1,150 men with mHSPC. Patients on this trial could have previously received ADT and/or up to 6 cycles of docetaxel chemotherapy, but could not have experienced disease progression on those therapies.
The addition of enzalutamide to ADT in men with mHSPC reduced the risk of radiographic disease progression (growth of tumors on scans) or death (whichever came first) by 61%, compared with placebo. Subgroup analysis of radiographic progression-free survival indicated enzalutamide was beneficial compared with placebo in low and high volume disease, and in men with and without prior docetaxel chemotherapy. Enzalutamide also significantly delayed time to PSA progression by 81%, and delayed the time to the next anticancer therapy by 72% compared with placebo. It is too early to evaluate overall survival (OS) in this trial as a median has not been reached for either treatment group.
Enzalutamide + ADT was well tolerated, with safety profiles consistent with previous trials testing enzalutamide in CRPC. Adverse events (AEs) that occurred more frequently in enzalutamide + ADT vs. placebo + ADT included: hot flash (27.1% vs 22.3%), fatigue (19.6% vs 15.3%), hypertension (8.0% vs 5.6%), and musculoskeletal pain (6.3% vs 4.0%). The total number of all grade AEs and Grade ≥3 AEs were similar in enzalutamide + ADT vs. placebo + ADT groups.
More information on this approval can be found here.