Malecare was actively involved, along with its partners, in setting up the early access trial for enzalutamide (Xtandi). The trial was conducted after the final Phase 3 AFFIRM trial that was eventually used to obtain FDA approval had been stopped, but before the FDA and received the final submission of the data. Given the significant positive results of the trial we felt that the drug needed to become available to those in need even though the FDA had not yet approved the treatment.
We accomplished this task by creating an Open-Label Single-Arm study to designed to monitor the drug’s safety while also providing access to enzalutamide for men with castrate resistant prostate cancer (mCRPC) pending marketing approval from the FDA.
We are proud to report that 507 men with mCRPC were treated at 54 sites. The trial participants received enzalutamide 160 mg/d in the study until disease progression, intolerable adverse event (AE), or it became commercially availability.
AEs, serious AEs (SAEs), vital signs, and laboratory measurements were assessed on day 1, week 4 and 12, and every 12 weeks thereafter. No efficacy data were collected as this was already submitted to the FDA from the actual AFFIRM trial itself
Median age of the men was 71 years (range 43-97). Baseline ECOG PS was 0, 1 and 2 in 27.8%, 56.1%, and 15.9% of the men, respectively.
Prior treatments for prostate cancer included abiraterone (Zytiga) (76.0%), and cabazitaxel (Jevtana) (28.6%); 24.8% of the men received both prior abiraterone and cabazitaxel.
Median enzalutamide treatment duration in the study was 2.6 months (range 0.03-9.07); data following transition to commercial drug was not collected.
Common AEs (?10%) included fatigue (39.1%), nausea (22.7%), anorexia (14.8%), anemia (11.8%), peripheral edema (11.4%), back pain (10.3%), vomiting (10.3%), and arthralgia (10.1%).
The SAEs reported in ?1% of the men were disease progression (7.9%), pneumonia (2.0%), asthenia (1.8%), anemia (1.6%), and back pain (1.4%). Drug-related AEs leading to permanent discontinuation occurred in 3.7% of the men.
Grade ?3 drug-related AEs were reported in 14.2 % of the men and drug-related AEs leading to death occurred in 4 men: 1 cerebrovascular accident, 2 myocardial infarctions and 1 death not otherwise specified. Seizure was reported in 4 (0.8%) men, of whom 3 had brain metastases.
In this expanded access population with progressive mCRPC who had previously received docetaxel, enzalutamide was well tolerated. The safety profile was consistent with that seen in the AFFIRM trial. Median treatment duration was shorter than in AFFIRM (2.6 vs. 8.3 months); duration on subsequent commercial drug was not collected.
The trial was a total success as we managed to have 507 men receive the yet unapproved treatment and the FDA was provided with additional safety data that could have been used in making the final decision to approve enzalutamide in the post chemotherapy stage of advanced prostate cancer.
Clinical trial information: NCT01606982.
Joel T. Nowak, M.A., M.S.W.